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Fontes MAP, Dos Santos Machado LR, Viana ACR, Cruz MH, Nogueira ÍS, Oliveira MGL, Neves CB, Godoy ACV, Henderson LA, Macefield VG. The insular cortex, autonomic asymmetry and cardiovascular control: looking at the right side of stroke. Clin Auton Res 2024; 34:549-560. [PMID: 39316247 DOI: 10.1007/s10286-024-01066-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 09/09/2024] [Indexed: 09/25/2024]
Abstract
PURPOSE Evidence from animal and human studies demonstrates that cortical regions play a key role in autonomic modulation with a differential role for some brain regions located in the left and right brain hemispheres. Known as autonomic asymmetry, this phenomenon has been demonstrated by clinical observations, by experimental models, and currently by combined neuroimaging and direct recordings of sympathetic nerve activity. Previous studies report peculiar autonomic-mediated cardiovascular alterations following unilateral damage to the left or right insula, a multifunctional key cortical region involved in emotional processing linked to autonomic cardiovascular control and featuring asymmetric characteristics. METHODS Based on clinical studies reporting specific damage to the insular cortex, this review aims to provide an overview of the prognostic significance of unilateral (left or right hemisphere) post-insular stroke cardiac alterations. In addition, we review experimental data aiming to unravel the central mechanisms involved in post-insular stroke cardiovascular complications. RESULTS AND CONCLUSION Current clinical and experimental data suggest that stroke of the right insula can present a worse cardiovascular prognosis.
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Affiliation(s)
- Marco Antônio Peliky Fontes
- Hypertension Laboratory, Department of Physiology and Biophysics - Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, 31270 901, Brazil.
| | - Liliane Ramos Dos Santos Machado
- Hypertension Laboratory, Department of Physiology and Biophysics - Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, 31270 901, Brazil
| | - Ana Clara Rocha Viana
- Hypertension Laboratory, Department of Physiology and Biophysics - Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, 31270 901, Brazil
| | - Matheus Henrique Cruz
- Hypertension Laboratory, Department of Physiology and Biophysics - Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, 31270 901, Brazil
| | - Ícaro Santos Nogueira
- Hypertension Laboratory, Department of Physiology and Biophysics - Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, 31270 901, Brazil
| | - Marcela Gondim Lima Oliveira
- Hypertension Laboratory, Department of Physiology and Biophysics - Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, 31270 901, Brazil
| | - Christiane Braga Neves
- Hypertension Laboratory, Department of Physiology and Biophysics - Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, 31270 901, Brazil
| | - Ana Caroline Ventris Godoy
- Hypertension Laboratory, Department of Physiology and Biophysics - Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, 31270 901, Brazil
| | | | - Vaughan G Macefield
- Department of Neuroscience, Monash University, Melbourne, Australia
- Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Australia
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Sato Y, Matsumoto M, Koganezawa T. The dopaminergic system mediates the lateral habenula-induced autonomic cardiovascular responses. Front Physiol 2024; 15:1496726. [PMID: 39640253 PMCID: PMC11617519 DOI: 10.3389/fphys.2024.1496726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Accepted: 11/11/2024] [Indexed: 12/07/2024] Open
Abstract
The lateral habenula (LHb) has been implicated in stress coping and autonomic control. The LHb regulates the midbrain system of monoamine neurotransmitters such as dopamine, serotonin, and noradrenaline. However, how the LHb regulates autonomic cardiovascular control in stressful situations is unclear. In this study, we examined the participation of the midbrain dopaminergic system in the cardiovascular response elicited by activation of the LHb. We used urethane-anesthetized Wistar male rats. We performed electrical stimulation of the LHb to observe changes in heart rate and blood pressure. Stimulation of the LHb caused bradycardia and a pressor response. Application of a nonselective dopamine receptor antagonist attenuated both the heart rate and the blood pressure changes induced by the LHb. We also tested the effects of blockade of dopamine receptor subtypes in the LHb-induced cardiovascular responses. Application of selective dopamine D1/D5, D2/D3, or D4 receptor antagonists attenuated the LHb-induced pressor response but did not change the HR response. Furthermore, we examined the effect of inactivation of the ventral tegmental area (VTA) on the cardiovascular response induced by LHb stimulation. Inactivation of the VTA turned bradycardia into tachycardia caused by the LHb stimulation and attenuated the pressor response. Our results indicated that regulation of the dopaminergic system by the LHb mediates the generation of the autonomic cardiovascular response. Dopamine D1-like and D2-like receptors mediate the sympathoexcitation resulting from the activation of the LHb. The VTA is one of the dopaminergic origins related to the cardiovascular response originating from LHb activation.
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Affiliation(s)
- Yuma Sato
- Department of Neurophysiology, Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
- Doctoral Program in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Masayuki Matsumoto
- Department of Cognitive and Behavioral Neuroscience, Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
- Center for the Evolutionary Origins of Human Behavior, Kyoto University, Inuyama, Aichi, Japan
| | - Tadachika Koganezawa
- Department of Neurophysiology, Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
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Carrillo-Franco L, González-García M, Morales-Luque C, Dawid-Milner MS, López-González MV. Hypothalamic Regulation of Cardiorespiratory Functions: Insights into the Dorsomedial and Perifornical Pathways. BIOLOGY 2024; 13:933. [PMID: 39596888 PMCID: PMC11592276 DOI: 10.3390/biology13110933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 11/08/2024] [Accepted: 11/14/2024] [Indexed: 11/29/2024]
Abstract
The dorsomedial hypothalamus nucleus (DMH) plays a pivotal role in the orchestration of sympathetic nervous system activities. Through its projections to the brainstem and pontomedullary nuclei, it controls heart rate, contractility, blood pressure, and respiratory activity, such as timing and volumes. The DMH integrates inputs from higher brain centers and processes these signals in order to modulate autonomic outflow accordingly. It has been demonstrated to be of particular significance in the context of stress responses, where it orchestrates the physiological adaptations that are necessary for all adaptative responses. The perifornical region (PeF), which is closely associated with the DMH, also makes a contribution to autonomic regulation. The involvement of the PeF region in autonomic control is evidenced by its function in coordinating the autonomic and endocrine responses to stress, frequently in conjunction with the DMH. The DMH and the PeF do not function in an isolated manner; rather, they are components of a comprehensive hypothalamic network that integrates several autonomic responses. This neural network could serve as a target for developing therapeutic strategies in cardiovascular diseases.
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Affiliation(s)
- Laura Carrillo-Franco
- Department of Human Physiology, Faculty of Medicine, University of Málaga, 29010 Malaga, Spain; (C.M.-L.); (M.S.D.-M.); (M.V.L.-G.)
- Unit of Neurophysiology of the Autonomic Nervous System (CIMES), University of Málaga, 29010 Malaga, Spain
- Biomedical Research Institute of Málaga (IBIMA Plataforma BIONAND), 29010 Malaga, Spain
| | - Marta González-García
- Department of Human Physiology, Faculty of Medicine, University of Málaga, 29010 Malaga, Spain; (C.M.-L.); (M.S.D.-M.); (M.V.L.-G.)
- Unit of Neurophysiology of the Autonomic Nervous System (CIMES), University of Málaga, 29010 Malaga, Spain
- Biomedical Research Institute of Málaga (IBIMA Plataforma BIONAND), 29010 Malaga, Spain
| | - Carmen Morales-Luque
- Department of Human Physiology, Faculty of Medicine, University of Málaga, 29010 Malaga, Spain; (C.M.-L.); (M.S.D.-M.); (M.V.L.-G.)
| | - Marc Stefan Dawid-Milner
- Department of Human Physiology, Faculty of Medicine, University of Málaga, 29010 Malaga, Spain; (C.M.-L.); (M.S.D.-M.); (M.V.L.-G.)
- Unit of Neurophysiology of the Autonomic Nervous System (CIMES), University of Málaga, 29010 Malaga, Spain
- Biomedical Research Institute of Málaga (IBIMA Plataforma BIONAND), 29010 Malaga, Spain
| | - Manuel Víctor López-González
- Department of Human Physiology, Faculty of Medicine, University of Málaga, 29010 Malaga, Spain; (C.M.-L.); (M.S.D.-M.); (M.V.L.-G.)
- Unit of Neurophysiology of the Autonomic Nervous System (CIMES), University of Málaga, 29010 Malaga, Spain
- Biomedical Research Institute of Málaga (IBIMA Plataforma BIONAND), 29010 Malaga, Spain
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Kim KT, Lee JH, Hong JP, Park JW, Lee SU, Park E, Kim BJ, Kim JS. Blood Pressure Variability and Ocular Vestibular-Evoked Myogenic Potentials Are Independently Associated With Orthostatic Hypotension. J Clin Neurol 2024; 20:571-579. [PMID: 39505309 PMCID: PMC11543387 DOI: 10.3988/jcn.2024.0092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 06/03/2024] [Accepted: 07/19/2024] [Indexed: 11/08/2024] Open
Abstract
BACKGROUND AND PURPOSE We delineated the association between otolithic dysfunction and blood pressure (BP) variability. METHODS We prospectively recruited 145 consecutive patients (age=71 [59-79] years, median [interquartile range]; 76 females) with orthostatic intolerance between December 2021 and December 2023 at a tertiary hospital in South Korea. Each patient underwent evaluations of cervical and ocular vestibular-evoked myogenic potentials (oVEMPs), 24-h noninvasive ambulatory BP monitoring (ABPM), and a head-up tilt-table test using the Finometer device. As measures of BP variability, the standard deviations (SDs) of the systolic BP (SBPSD) and the diastolic BP were calculated based on serial ABPM recordings. Patients were divided into those with orthostatic hypotension (OH, n=68) and those with a normal head-up tilt-table test despite orthostatic intolerance (NOI, n=77) groups. RESULTS A multivariable logistic regression analysis showed that OH was associated with bilateral oVEMP abnormalities (p=0.021), SBPSD (p=0.012), and female sex (p=0.004). SBPSD was higher in patients with OH than in those with NOI (p<0.001), and was not correlated with n1-p1 amplitude (p=0.491) or normalized p13-n23 amplitude (p=0.193) in patients with OH. The sensitivity and specificity for differentiating OH from NOI were 72.1% and 67.5%, respectively, at a cutoff value of 12.7 mm Hg for SBPSD, with an area under the receiver operating characteristic curve of 0.73. CONCLUSIONS Bilaterally deficient oVEMP responses may be associated with OH regardless of 24-h BP variability, reflecting the integrity of the otolith-autonomic reflex during orthostasis. Alternatively, 24-h BP variability is predominantly regulated by the baroreflex, which also participates in securing orthostatic tolerance complementary to the vestibulo-autonomic reflex.
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Affiliation(s)
- Keun-Tae Kim
- Department of Neurology, Korea University Medical Center, Seoul, Korea
| | - Jeong-Heon Lee
- Department of Neurology, Korea University Medical Center, Seoul, Korea
| | - Jun-Pyo Hong
- Department of Neurology, Korea University Medical Center, Seoul, Korea
| | - Jin-Woo Park
- Department of Neurology, Korea University Medical Center, Seoul, Korea
| | - Sun-Uk Lee
- Department of Neurology, Korea University Medical Center, Seoul, Korea
- Neurotology and Neuro-ophthalmology Laboratory, Korea University Medical Center, Seoul, Korea.
| | - Euyhyun Park
- Neurotology and Neuro-ophthalmology Laboratory, Korea University Medical Center, Seoul, Korea
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea
| | - Byung-Jo Kim
- Department of Neurology, Korea University Medical Center, Seoul, Korea
- BK21 FOUR Program in Learning Health Systems, Korea University, Seoul, Korea
| | - Ji-Soo Kim
- Dizziness Center, Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Neurology, Seoul National University College of Medicine, Seoul, Korea
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Costa PCT, de Luna Freire MO, de Oliveira Coutinho D, Godet M, Magnani M, Antunes VR, de Souza EL, Vidal H, de Brito Alves JL. Nutraceuticals in the management of autonomic function and related disorders: A comprehensive review. Pharmacol Res 2024; 208:107368. [PMID: 39191337 DOI: 10.1016/j.phrs.2024.107368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 07/31/2024] [Accepted: 08/21/2024] [Indexed: 08/29/2024]
Abstract
Nutraceuticals have been described as phytocomplexes when derived from foods of plant origin or a pool of secondary metabolites when derived from foods of animal origin, which are concentrated and administered in an appropriate form and can promote beneficial health effects in the prevention/treatment of diseases. Considering that pharmaceutical medications can cause side effects, there is a growing interest in using nutraceuticals as an adjuvant therapeutic tool for several disorders involving autonomic dysfunction, such as obesity, atherosclerosis and other cardiometabolic diseases. This review summarizes and discusses the evidence from the literature on the effects of various nutraceuticals on autonomic control, addressing the gut microbiota modulation, production of secondary metabolites from bioactive compounds, and improvement of physical and chemical properties of cell membranes. Additionally, the safety of nutraceuticals and prospects are discussed. Probiotics, resveratrol, quercetin, curcumin, nitrate, inositol, L-carnosine, and n-3 polyunsaturated fatty acids (n-3 PUFAs) are among the nutraceuticals most studied to improve autonomic dysfunction in experimental animal models and clinical trials. Further human studies are needed to elucidate the effects of nutraceuticals formulated of multitarget compounds and their underlying mechanisms of action, which could benefit conditions involving autonomic dysfunction.
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Affiliation(s)
- Paulo César Trindade Costa
- Department of Nutrition, Federal University of Paraíba, João Pessoa, PB, Brazil; Laboratoire CarMeN, INSERM U.1060, INRAe U. 1397, Université Claude Bernard Lyon1, Pierre Bénite, France
| | | | | | - Murielle Godet
- Laboratoire CarMeN, INSERM U.1060, INRAe U. 1397, Université Claude Bernard Lyon1, Pierre Bénite, France
| | - Marciane Magnani
- Department of Food Engineering, Federal University of Paraíba, João Pessoa, PB, Brazil
| | - Vagner Roberto Antunes
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
| | | | - Hubert Vidal
- Laboratoire CarMeN, INSERM U.1060, INRAe U. 1397, Université Claude Bernard Lyon1, Pierre Bénite, France
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Weizman L, Sharon H, Dayan L, Espaniol J, Brill S, Nahman-Averbuch H, Hendler T, Jacob G. Oral Delta-9-Tetrahydrocannabinol (THC) Increases Parasympathetic Activity and Supraspinal Conditioned Pain Modulation in Chronic Neuropathic Pain Male Patients: A Crossover, Double-Blind, Placebo-Controlled Trial. CNS Drugs 2024; 38:375-385. [PMID: 38597988 PMCID: PMC11026292 DOI: 10.1007/s40263-024-01085-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/11/2024] [Indexed: 04/11/2024]
Abstract
BACKGROUND Disordered autonomic nervous system regulation and supraspinal pain inhibition have been repeatedly described in chronic pain. We aimed to explore the effects of δ-9-tetrahydrocannabinol (THC), an emerging treatment option, on autonomic nervous system and central pain modulation measures in patients with chronic pain. METHODS Twelve male patients with chronic radicular neuropathic pain participated in a randomized, double-blind, crossover, placebo-controlled, single-administration trial. Low/high frequency (LF/HF) heart rate variability (HRV) ratio and conditioned pain modulation (CPM) response were measured and resting-state functional magnetic resonance imaging (MRI) was performed at baseline and after sublingual administration of either 0.2 mg/kg oral THC or placebo. RESULTS THC significantly reduced the LF/HF ratio compared with placebo (interaction effect F(1,11) = 20.5; p < 0.005) and significantly improved CPM responses (interaction effect F(1,9) = 5.2; p = 0.048). The THC-induced reduction in LF/HF ratio correlated with increased functional connectivity between the rostral ventrolateral medulla and the dorsolateral prefrontal cortex [T(10) = 6.4, cluster p-FDR < 0.005]. CONCLUSIONS THC shifts the autonomic balance towards increased parasympathetic tone and improves inhibitory pain mechanisms in chronic pain. The increase in vagal tone correlates with connectivity changes in higher-order regulatory brain regions, suggesting THC exerts top-down effects. These changes may reflect a normalizing effect of THC on multiple domains of supraspinal pain dysregulation. CLINICAL TRIAL REGISTRY NUMBER NCT02560545.
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Affiliation(s)
- Libat Weizman
- Sagol Brain Institute, Wohl Institute for Advanced Imaging, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Haggai Sharon
- Sagol Brain Institute, Wohl Institute for Advanced Imaging, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
- School of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Anesthesiology and Critical Care Medicine, Institute of Pain Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Lior Dayan
- Department of Anesthesiology and Critical Care Medicine, Institute of Pain Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Joumana Espaniol
- Department of Internal Medicine F, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
- Recanati Autonomic Dysfunction Center, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Silviu Brill
- Department of Anesthesiology and Critical Care Medicine, Institute of Pain Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Hadas Nahman-Averbuch
- Division of Clinical and Translational Research, Department of Anesthesiology, Washington University Pain Center, Washington University in St Louis School of Medicine, St Louis, MO, USA
| | - Talma Hendler
- Sagol Brain Institute, Wohl Institute for Advanced Imaging, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
- School of Medicine, Tel Aviv University, Tel Aviv, Israel
- School of Psychological Sciences, Tel Aviv University, Tel-Aviv, Israel
| | - Giris Jacob
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
- School of Medicine, Tel Aviv University, Tel Aviv, Israel.
- Department of Internal Medicine F, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
- Recanati Autonomic Dysfunction Center, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
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Bernardo EM, Pedroza AADS, Ferreira DJS, de Andrade SC, Rozendo A, Fernandes MSDS, Silva TL, Fernandes MP, Lagranha CJ. The deleterious effects of maternal protein deprivation on the brainstem are minimized with moderate physical activity by offspring during early life. Appl Physiol Nutr Metab 2024; 49:157-166. [PMID: 37816257 DOI: 10.1139/apnm-2023-0122] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/12/2023]
Abstract
Maternal protein malnutrition during developmental periods might impair the redox state and the brain's excitatory/inhibitory neural network, increasing central sympathetic tone. Conversely, moderate physical exercise at an early age reduces the risk of chronic diseases. Thus, we hypothesized that a moderate training protocol could reduce the harmful effects of a low-protein maternal diet on the brainstem of young male offspring. We used a rat model of maternal protein restriction during the gestational and lactation period followed by an offspring's continuous treadmill exercise. Pregnant rats were divided into two groups according to the protein content in the diet: normoprotein (NP), receiving 17% of casein, and low protein (LP), receiving 8% of casein until the end of lactation. At 30 days of age, the male offspring were further subdivided into sedentary (NP-Sed and LP-Sed) or exercised (NP-Ex and LP-Ex) groups. Treadmill exercise was performed as follows: 4 weeks, 5 days/week, 60 min/day at 50% of maximal running capacity. The trained animals performed a treadmill exercise at 50% of the maximal running capacity, 60 min/day, 5 days/week, for 4 weeks. Our results indicate that a low-protein diet promotes deficits in the antioxidant system and a likely mitochondrial uncoupling. On the other hand, physical exercise restores the redox balance, which leads to decreased oxidative stress caused by the diet. In addition, it also promotes benefits to GABAergic inhibitory signaling. We conclude that regular moderate physical exercise performed in youthhood protects the brainstem against changes induced by maternal protein restriction.
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Affiliation(s)
| | | | | | - Severina Cassia de Andrade
- Neuropsyquiatry and Behavioral Science Graduate Program, Federal University of Pernambuco (UFPE), Recife, Pernambuco, Brazil
| | - Allifer Rozendo
- Laboratory of Biochemistry and Exercise Biochemistry/CAV, Federal University of Pernambuco, Vitoria de Santo Antao, PE, Brazil
| | | | - Tercya Lucidi Silva
- Neuropsyquiatry and Behavioral Science Graduate Program, Federal University of Pernambuco (UFPE), Recife, Pernambuco, Brazil
| | - Mariana Pinheiro Fernandes
- Laboratory of Biochemistry and Exercise Biochemistry/CAV, Federal University of Pernambuco, Vitoria de Santo Antao, PE, Brazil
| | - Claudia J Lagranha
- Biochemistry and Physiology Graduate Program, Federal University of Pernambuco, Recife, PE, Brazil
- Neuropsyquiatry and Behavioral Science Graduate Program, Federal University of Pernambuco (UFPE), Recife, Pernambuco, Brazil
- Laboratory of Biochemistry and Exercise Biochemistry/CAV, Federal University of Pernambuco, Vitoria de Santo Antao, PE, Brazil
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Zahner MR, Brown MC, Chandley MJ. Inactivation of the paraventricular nucleus attenuates the cardiogenic sympathetic afferent reflex in the spontaneously hypertensive rat. J Hypertens 2024; 42:70-78. [PMID: 37889604 PMCID: PMC10792548 DOI: 10.1097/hjh.0000000000003542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/29/2023]
Abstract
BACKGROUND Myocardial ischemia causes the release of bradykinin, which stimulates cardiac afferents, causing sympathetic excitation and chest pain. Glutamatergic activation of the paraventricular hypothalamic nucleus (PVN) in the spontaneously hypertensive rat (SHR) drives elevated basal sympathetic activity. Thus, we tested the hypothesis that inactivation of the PVN attenuates the elevated reflex response to epicardial bradykinin in the SHR and that ionotropic PVN glutamate receptors mediate the elevated reflex. METHODS We recorded the arterial pressure and renal sympathetic nerve activity (RSNA) response to epicardial bradykinin application in anesthetized SHR and Wistar Kyoto (WKY) rats before and after PVN microinjection of GABA A agonist muscimol or ionotropic glutamate receptor antagonist kynurenic acid. RESULTS Muscimol significantly decreased the arterial pressure response to bradykinin from 180.4 ± 5.8 to 119.5 ± 6.9 mmHg in the SHR and from 111.8 ± 7.0 to 84.2 ± 8.3 mmHg in the WKY and the RSNA response from 186.2 ± 7.1 to 142.7 ± 7.3% of baseline in the SHR and from 201.0 ± 11.5 to 160.2 ± 9.3% of baseline in the WKY. Kynurenic acid significantly decreased the arterial pressure response in the SHR from 164.5 ± 5.0 to 126.2 ± 7.7 mmHg and the RSNA response from 189.9 ± 13.7to 168.5 ± 12.7% of baseline but had no effect in the WKY. CONCLUSION These results suggest that tonic PVN activity is critical for the full manifestation of the CSAR in both the WKY and SHR. Glutamatergic PVN activity contributes to the augmented CSAR observed in the SHR.
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Affiliation(s)
- Matthew R Zahner
- Department of Health Sciences, East Tennessee State University College of Public Health
| | - Mary C Brown
- Department of Health Sciences, East Tennessee State University College of Public Health
| | - Michelle J Chandley
- Department of Biomedical Science, East Tennessee State University College of Medicine, Johnson City, Tennessee, USA
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Schumann A, Gupta Y, Gerstorf D, Demuth I, Bär KJ. Sex differences in the age-related decrease of spontaneous baroreflex function in healthy individuals. Am J Physiol Heart Circ Physiol 2024; 326:H158-H165. [PMID: 37947436 DOI: 10.1152/ajpheart.00648.2023] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 11/07/2023] [Accepted: 11/07/2023] [Indexed: 11/12/2023]
Abstract
The baroreflex is a powerful physiological mechanism for rapidly adjusting heart rate in response to changes in blood pressure. Spontaneous baroreflex sensitivity (BRS) has been shown to decrease with age. However, studies of sex differences in these age-related changes are rare. Here we investigated several markers of spontaneous baroreflex function in a large sample of healthy individuals. Cardiovascular signals were recorded in the supine position under carefully controlled resting conditions. After quality control, n = 980 subjects were divided into five age groups [age < 30 yr (n = 612), 30-39 yr (n = 140), 40-49 yr (n = 95), 50-59 yr (n = 61), and >60 yr (n = 72)]. Spontaneous baroreflex function was assessed in the time domain (bradycardic and tachycardic slope) and in the frequency domain in the low- and high-frequency band (LF-α, HF-α) applying the transfer function. General linear models showed a significant effect of factor age (P < 0.001) and an age × sex interaction effect (P < 0.05) on each indicator of the baroreflex function. Simple main effects showed a significantly higher BRS as indicated by tachycardic slope, LF-α and HF-α in middle-aged women compared with men (30-39 yr) and higher LF-α, bradycardic and tachycardic slope in men compared with women of the oldest age group (>60 yr). Changes in BRS over the lifespan suggest that baroreflex function declines more slowly but earlier in life in men than in women. Our findings could be linked to age-related changes in major sex hormone levels, suggesting significant implications for diverse cardiovascular outcomes and the implementation of targeted preventive strategies.NEW & NOTEWORTHY In this study, we demonstrate that the age-related decrease of spontaneous baroreflex sensitivity is different in men and women by analyzing resting state cardiovascular data of a large sample of healthy individuals.
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Affiliation(s)
- Andy Schumann
- Lab for Autonomic Neuroscience, Imaging and Cognition, Department for Psychosomatic Medicine and Psychotherapy, Jena University Hospital, Jena, Germany
| | - Yubraj Gupta
- Lab for Autonomic Neuroscience, Imaging and Cognition, Department for Psychosomatic Medicine and Psychotherapy, Jena University Hospital, Jena, Germany
| | - Denis Gerstorf
- Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Ilja Demuth
- Department of Endocrinology and Metabolic Diseases, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Karl-Jürgen Bär
- Lab for Autonomic Neuroscience, Imaging and Cognition, Department for Psychosomatic Medicine and Psychotherapy, Jena University Hospital, Jena, Germany
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10
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Fontes MAP, Marins FR, Patel TA, de Paula CA, Dos Santos Machado LR, de Sousa Lima ÉB, Ventris-Godoy AC, Viana ACR, Linhares ICS, Xavier CH, Filosa JA, Patel KP. Neurogenic Background for Emotional Stress-Associated Hypertension. Curr Hypertens Rep 2023; 25:107-116. [PMID: 37058193 PMCID: PMC10103037 DOI: 10.1007/s11906-023-01235-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2023] [Indexed: 04/15/2023]
Abstract
PURPOSE OF REVIEW The response to natural stressors involves both cardiac stimulation and vascular changes, primarily triggered by increases in sympathetic activity. These effects lead to immediate flow redistribution that provides metabolic support to priority target organs combined with other key physiological responses and cognitive strategies, against stressor challenges. This extremely well-orchestrated response that was developed over millions of years of evolution is presently being challenged, over a short period of time. In this short review, we discuss the neurogenic background for the origin of emotional stress-induced hypertension, focusing on sympathetic pathways from related findings in humans and animals. RECENT FINDINGS The urban environment offers a variety of psychological stressors. Real or anticipatory, emotional stressors may increase baseline sympathetic activity. From routine day-to-day traffic stress to job-related anxiety, chronic or abnormal increases in sympathetic activity caused by emotional stressors can lead to cardiovascular events, including cardiac arrhythmias, increases in blood pressure and even sudden death. Among the various alterations proposed, chronic stress could modify neuroglial circuits or compromise antioxidant systems that may alter the responsiveness of neurons to stressful stimuli. These phenomena lead to increases in sympathetic activity, hypertension and consequent cardiovascular diseases. The link between anxiety, emotional stress, and hypertension may result from an altered neuronal firing rate in central pathways controlling sympathetic activity. The participation of neuroglial and oxidative mechanisms in altered neuronal function is primarily involved in enhanced sympathetic outflow. The significance of the insular cortex-dorsomedial hypothalamic pathway in the evolution of enhanced overall sympathetic outflow is discussed.
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Affiliation(s)
- Marco Antônio Peliky Fontes
- Department of Physiology & Biophysics, Federal University of Minas Gerais, Federal de Minas Gerais, Belo Horizonte, MG, 31270 901, Brazil.
| | - Fernanda Ribeiro Marins
- Department of Physiology & Biophysics, Federal University of Minas Gerais, Federal de Minas Gerais, Belo Horizonte, MG, 31270 901, Brazil
| | - Tapan A Patel
- Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Cristiane Amorim de Paula
- Department of Physiology & Biophysics, Federal University of Minas Gerais, Federal de Minas Gerais, Belo Horizonte, MG, 31270 901, Brazil
| | - Liliane Ramos Dos Santos Machado
- Department of Physiology & Biophysics, Federal University of Minas Gerais, Federal de Minas Gerais, Belo Horizonte, MG, 31270 901, Brazil
| | - Érick Bryan de Sousa Lima
- Department of Physiology & Biophysics, Federal University of Minas Gerais, Federal de Minas Gerais, Belo Horizonte, MG, 31270 901, Brazil
| | - Ana Caroline Ventris-Godoy
- Department of Physiology & Biophysics, Federal University of Minas Gerais, Federal de Minas Gerais, Belo Horizonte, MG, 31270 901, Brazil
| | - Ana Clara Rocha Viana
- Department of Physiology & Biophysics, Federal University of Minas Gerais, Federal de Minas Gerais, Belo Horizonte, MG, 31270 901, Brazil
| | - Isadora Cristina Souza Linhares
- Department of Physiology & Biophysics, Federal University of Minas Gerais, Federal de Minas Gerais, Belo Horizonte, MG, 31270 901, Brazil
| | | | | | - Kaushik P Patel
- Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA
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11
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Bravo-Iñiguez CE, Fritz JR, Shukla S, Sarangi S, Thompson DA, Amin SG, Tsaava T, Chaudhry S, Valentino SP, Hoffman HB, Imossi CW, Addorisio ME, Valdes-Ferrer SI, Chavan SS, Blanc L, Czura CJ, Tracey KJ, Huston JM. Vagus nerve stimulation primes platelets and reduces bleeding in hemophilia A male mice. Nat Commun 2023; 14:3122. [PMID: 37264009 PMCID: PMC10235098 DOI: 10.1038/s41467-023-38505-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 05/05/2023] [Indexed: 06/03/2023] Open
Abstract
Deficiency of coagulation factor VIII in hemophilia A disrupts clotting and prolongs bleeding. While the current mainstay of therapy is infusion of factor VIII concentrates, inhibitor antibodies often render these ineffective. Because preclinical evidence shows electrical vagus nerve stimulation accelerates clotting to reduce hemorrhage without precipitating systemic thrombosis, we reasoned it might reduce bleeding in hemophilia A. Using two different male murine hemorrhage and thrombosis models, we show vagus nerve stimulation bypasses the factor VIII deficiency of hemophilia A to decrease bleeding and accelerate clotting. Vagus nerve stimulation targets acetylcholine-producing T lymphocytes in spleen and α7 nicotinic acetylcholine receptors (α7nAChR) on platelets to increase calcium uptake and enhance alpha granule release. Splenectomy or genetic deletion of T cells or α7nAChR abolishes vagal control of platelet activation, thrombus formation, and bleeding in male mice. Vagus nerve stimulation warrants clinical study as a therapy for coagulation disorders and surgical or traumatic bleeding.
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Affiliation(s)
- Carlos E Bravo-Iñiguez
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
- Elmezzi Graduate School of Molecular Medicine at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Jason R Fritz
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Shilpa Shukla
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
- Department of Pediatric Hematology and Oncology, Cohen Children's Medical Center, Northwell Health, Lake Success, NY, 11040, USA
| | - Susmita Sarangi
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
- Department of Pediatric Hematology and Oncology, Cohen Children's Medical Center, Northwell Health, Lake Success, NY, 11040, USA
| | - Dane A Thompson
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
- Elmezzi Graduate School of Molecular Medicine at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
- Department of Surgery, Northwell Health, 300 Community Drive, Manhasset, NY, 11030, USA
| | - Seema G Amin
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
- Department of Pediatric Hematology and Oncology, Cohen Children's Medical Center, Northwell Health, Lake Success, NY, 11040, USA
| | - Tea Tsaava
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Saher Chaudhry
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Sara P Valentino
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Hannah B Hoffman
- Department of Surgery, Northwell Health, 300 Community Drive, Manhasset, NY, 11030, USA
| | - Catherine W Imossi
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Meghan E Addorisio
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Sergio I Valdes-Ferrer
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Sangeeta S Chavan
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
- Elmezzi Graduate School of Molecular Medicine at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Lionel Blanc
- Elmezzi Graduate School of Molecular Medicine at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
- Institute of Molecular Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
- Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
- Departments of Molecular Medicine and Pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 500 Hofstra Boulevard, Hempstead, NY, 11549, USA
| | - Christopher J Czura
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Kevin J Tracey
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
- Elmezzi Graduate School of Molecular Medicine at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA
| | - Jared M Huston
- Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY, 11030, USA.
- Department of Surgery, Northwell Health, 300 Community Drive, Manhasset, NY, 11030, USA.
- Department of Science Education, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 500 Hofstra Boulevard, Hempstead, NY, 11549, USA.
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12
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Paeslack N, Mimmler M, Becker S, Gao Z, Khuu MP, Mann A, Malinarich F, Regen T, Reinhardt C. Microbiota-derived tryptophan metabolites in vascular inflammation and cardiovascular disease. Amino Acids 2022; 54:1339-1356. [PMID: 35451695 PMCID: PMC9641817 DOI: 10.1007/s00726-022-03161-5] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 03/27/2022] [Indexed: 12/17/2022]
Abstract
The essential amino acid tryptophan (Trp) is metabolized by gut commensals, yielding in compounds that affect innate immune cell functions directly, but also acting on the aryl hydrocarbon receptor (AHR), thus regulating the maintenance of group 3 innate lymphoid cells (ILCs), promoting T helper 17 (TH17) cell differentiation, and interleukin-22 production. In addition, microbiota-derived Trp metabolites have direct effects on the vascular endothelium, thus influencing the development of vascular inflammatory phenotypes. Indoxyl sulfate was demonstrated to promote vascular inflammation, whereas indole-3-propionic acid and indole-3-aldehyde had protective roles. Furthermore, there is increasing evidence for a contributory role of microbiota-derived indole-derivatives in blood pressure regulation and hypertension. Interestingly, there are indications for a role of the kynurenine pathway in atherosclerotic lesion development. Here, we provide an overview on the emerging role of gut commensals in the modulation of Trp metabolism and its influence in cardiovascular disease development.
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Affiliation(s)
- Nadja Paeslack
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany
| | - Maximilian Mimmler
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany
| | - Stefanie Becker
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany
| | - Zhenling Gao
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany
| | - My Phung Khuu
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany
| | - Amrit Mann
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany
| | - Frano Malinarich
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany
| | - Tommy Regen
- Institute for Molecular Medicine, University Medical Center Mainz, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany
| | - Christoph Reinhardt
- Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany.
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany.
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13
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Low intensity stimulation of aortic baroreceptor afferent fibers as a potential therapeutic alternative for hypertension treatment. Sci Rep 2022; 12:12242. [PMID: 35851099 PMCID: PMC9293925 DOI: 10.1038/s41598-022-15761-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 06/29/2022] [Indexed: 11/17/2022] Open
Abstract
Carotid baroreceptor stimulation has been clinically explored for antihypertensive benefits, but neuromodulation of aortic baroreceptor afferents remains unexplored for potential translation into the clinic. Published studies have used supramaximal stimulations, which are unphysiological and energy inefficient. The objective of the present study was to identify optimal low-charge nerve stimulation parameters that would provide a clinically-relevant (20–30 mmHg) decrease in mean arterial pressure (MAP) in anesthetized spontaneously hypertensive rats. Stimulations of 20 s were delivered to the left aortic depressor nerve (ADN) of these rats using low ranges of pulse amplitudes (≤ 0.6 mA), widths (≤ 0.5 ms) and frequencies (≤ 5 Hz). We also assessed the effects of continuous (20 s) versus intermittent (5 s ON/3 s OFF and 5 s ON/3 s OFF for 20 s) stimulation on MAP, heart rate (HR), mesenteric (MVR) and femoral (FVR) vascular resistance using low (5 Hz) and high (15 Hz) frequencies. Lower pulse amplitudes (0.2 mA) produced 9 ± 2 to 18 ± 2 mmHg decreases in MAP. Higher pulse amplitudes (0.4 mA) produced a median MAP reduction of 28 ± 4 mmHg at 0.2 ms and 5 Hz, with no added benefit seen above 0.4 mA. Continuous and intermittent low frequency stimulation at 0.4 mA and 0.2 ms produced similar sustained decreases in MAP, HR, MVR and FVR. Continuous high frequency stimulation at 0.4 mA and 0.2 ms produced larger reductions in MAP, HR, MVR and FVR compared with all low frequency and/or intermittent high frequency stimulations. We conclude from these findings that “low intensity intermittent” electrical stimulation is an effective alternate way for neuromodulation of the aortic baroreceptor afferents and to evoke a required restoration of MAP levels in spontaneously hypertensive rats. This approach enables low energy consumption and markedly lowers the excessive decreases in MAP and hemodynamic disturbances elicited by continuous high-charge injection protocols.
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14
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Inchan A, Pathomwichaiwat T, Bualeong T, Tipratchadaporn S, Chootip K. Anti-hypotensive effect of “Yahom Navakot” in rats with orthostatic hypotension. J Tradit Complement Med 2022; 12:180-189. [PMID: 35528473 PMCID: PMC9072801 DOI: 10.1016/j.jtcme.2021.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 08/02/2021] [Accepted: 08/02/2021] [Indexed: 11/29/2022] Open
Abstract
Background and aim Yahom Navakot (YN), is a Thai traditional medicine, consisting of 54 plants, for treating fainting and dizziness. Thus, YN might relieve orthostatic hypotension (OH) symptoms, but its therapeutic action is unclear. Therefore, this study evaluated YN in OH rats, using a head-up tilt test (HUT). Experimental procedure Rats were anesthetized, and OH induced via a 90oHUT, before and after administering vehicle, a YN powder suspension (10, 100 mg/kg), a YN aqueous extract (100 mg/kg), and midodrine (5 mg/kg). The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), pulse pressure (PP) and heart rate (HR) were determined via the carotid artery. Plasma noradrenaline (NA) was evaluated. YN-induced vasoconstriction of isolated rat aorta rings was determined using organ bath technique. Results and conclusion Baseline BP increased with the 100 mg/kg YN powder suspension, the YN aqueous extract or midodrine, while HR decreased, compared with vehicle and control. 90oHUT rapidly reduced SBP, DPB and MAP, but increased HR, for control and vehicle-treated groups, but BP was steady with the 100 mg/kg YN powder suspension, the YN aqueous extract or midodrine. The 90oHUT-increase in HR was most pronounced with the 100 mg/kg YN powder suspension (the traditional formulation). This accords with increased plasma NA. YN also induced vasoconstriction in rat aorta via α1-receptor activation. Thus, the anti-hypotensive action of YN involved a stimulating effect on the heart and blood vessels via sympathetic activation. The results support the traditional use of YN and demonstrated the effectiveness of YN for OH prevention.
Yahom Navakot is an effective treatment for orthostatic hypotension. Yahom Navakot possesses chronotropic effect and vasoconstrictor action. Yahom Navakot increases plasma noradrenaline leading to the increase in blood pressure.
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Affiliation(s)
- Anjaree Inchan
- Department of Physiology, Faculty of Medical Science and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, 65000, Thailand
| | - Thanika Pathomwichaiwat
- Department of Pharmaceutical Botany, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand
- Sireeruckhachati Nature Learning Park, Mahidol University, 999 Phuttamonthon 4 Road, Salaya Phuttamonthon, Nakhon Pathom, 73170, Thailand
| | - Tippaporn Bualeong
- Department of Physiology, Faculty of Medical Science and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, 65000, Thailand
| | | | - Krongkarn Chootip
- Department of Physiology, Faculty of Medical Science and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, 65000, Thailand
- Corresponding author.
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15
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Tong L, Xing M, Wu J, Zhang S, Chu D, Zhang H, Chen F, Du D. Overexpression of NaV1.6 in the rostral ventrolateral medulla in rats mediates stress-induced hypertension via glutamate regulation. Clin Exp Hypertens 2022; 44:134-145. [PMID: 34994674 DOI: 10.1080/10641963.2021.2007942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
BACKGROUND The rostral ventrolateral medulla (RVLM) plays a key role in mediating the development of stress-induced hypertension (SIH). Furthermore, enhanced glutamate transport within glutamatergic neurons in the RVLM mediates pressor responses. Data from our previous studies suggest that the voltage-gated sodium channel NaV1.6 is overexpressed in neurons in the RVLM in SIH model rats and participates in the resulting elevation of blood pressure. However, previous studies have not investigated the relationship between NaV1.6 expression and glutamatergic neurons. METHODS Here, we constructed an SIH rat model by knocking down NaV1.6 via microinjection of clustered regularly interspaced short palindromic repeats (CRISPR) guide RNA into the RVLM. Glutamate-related markers were quantified by Western blotting and immunofluorescence, and blood pressure was measured in the rats. RESULTS Our findings showed that vesicular glutamate transporter 1 (VGluT1) protein expression in the RVLM was higher in SIH rats than in Control rats, and GAD67 protein expression in SIH rats was lower than that in Control rats. Therefore, the number of VGluT1-positive neurons increased, while the number of GAD67-labeled neurons decreased after stress. After knocking down NaV1.6 expression in the RVLM, VGluT1 expression and the number of VGluT1-positive neurons decreased relative to those in SIH rats, while GAD67 protein expression and the number of GAD67-labeled neurons increased relative to those in SIH rats. CONCLUSIONS These results indicate that overexpression of NaV1.6 in the RVLM may mediate the transport and transformation of glutamate in neurons, and NaV1.6 may participate in SIH.
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Affiliation(s)
- Lei Tong
- College of Life Science, Shanghai University, Shanghai, China
| | - Mengyu Xing
- College of Life Science, Shanghai University, Shanghai, China
| | - Jiaxiang Wu
- College of Life Science, Shanghai University, Shanghai, China
| | - Shuai Zhang
- International Cooperation Laboratory of Molecular Medicine, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Dechang Chu
- College of Agriculture and Bioengineering, Heze University, Heze, China
| | - Haili Zhang
- College of Agriculture and Bioengineering, Heze University, Heze, China
| | - Fuxue Chen
- College of Life Science, Shanghai University, Shanghai, China
| | - Dongshu Du
- College of Life Science, Shanghai University, Shanghai, China.,College of Agriculture and Bioengineering, Heze University, Heze, China
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16
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Thrivikraman KV, Kinkead B, Owens MJ, Rapaport MH, Plotsky PM. Locus Coeruleus Noradrenergic Modulation of Diurnal Corticosterone, Stress Reactivity, and Cardiovascular Homeostasis in Male Rats. Neuroendocrinology 2022; 112:763-776. [PMID: 34649254 PMCID: PMC9037608 DOI: 10.1159/000520192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 10/13/2021] [Indexed: 01/03/2023]
Abstract
INTRODUCTION Activation of the locus coeruleus-noradrenergic (LC-NA) system during awakening is associated with an increase in plasma corticosterone and cardiovascular tone. These studies evaluate the role of the LC in this corticosterone and cardiovascular response. METHODS Male rats, on day 0, were treated intraperitoneally with either DSP4 (50 mg/kg body weight) (DSP), an LC-NA specific neurotoxin, or normal saline (SAL). On day 10, animals were surgically prepared with jugular vein (hypothalamic-pituitary-adrenal [HPA] axis) or carotid artery (hemodynamics) catheters and experiments performed on day 14. HPA axis activity, diurnally (circadian) and after stress (transient hemorrhage [14 mL/kg body weight] or air puff-startle), and basal and post-hemorrhage hemodynamics were evaluated. On day 16, brain regions from a subset of rats were dissected for norepinephrine and corticotropin-releasing factor (CRF) assay. RESULTS In DSP rats compared to SAL rats, (1) regional brain norepinephrine was decreased, but there was no change in median eminence or olfactory bulb CRF content; (2) during HPA axis acrophase, the plasma corticosterone response was blunted; (3) after hemorrhage and air puff-startle, the plasma adrenocorticotropic hormone response was attenuated, whereas the corticosterone response was dependent on stressor category; (4) under basal conditions, hemodynamic measures exhibited altered blood flow dynamics and systemic vasodilation; and (5) after hemorrhage, hemodynamics exhibited asynchronous responses. CONCLUSION LC-NA modulation of diurnal and stress-induced HPA axis reactivity occurs via distinct neurocircuits. The integrity of the LC-NA system is important to maintain blood flow dynamics. The importance of increases in plasma corticosterone at acrophase to maintain short- and long-term cardiovascular homeostasis is discussed.
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Affiliation(s)
- K. V. Thrivikraman
- Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Becky Kinkead
- Huntsman Mental Health Institute, Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT 84108, USA
| | - Michael J. Owens
- Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Mark H. Rapaport
- Huntsman Mental Health Institute, Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT 84108, USA
| | - Paul M. Plotsky
- Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
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17
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Yilmaz A, Kalsbeek A, Buijs RM. Early changes of immunoreactivity to orexin in hypothalamus and to RFamide peptides in brainstem during the development of hypertension. Neurosci Lett 2021; 762:136144. [PMID: 34332031 DOI: 10.1016/j.neulet.2021.136144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 07/24/2021] [Accepted: 07/26/2021] [Indexed: 11/19/2022]
Abstract
Baroreflex sensitivity (BRS) is an important function of the nervous system and essential for maintaining blood pressure levels in the physiological range. In hypertension, BRS is decreased both in man and animals. Although increased sympathetic activity is thought to be the main cause of decreased BRS, hence the development of hypertension, the BRS is regulated by both sympathetic (SNS) and parasympathetic (PNS) nervous system. Here, we analyzed neuropeptide changes in the lateral hypothalamus (LH), which favours the SNS activity, as well as in PNS nuclei in the brainstem of spontaneously hypertensive rats (SHR) and their normotensive controls (Wistar Kyoto rats- WKY). The analyses revealed that in the WKY rats the hypothalamic orexin system, known for its role in sympathetic activation, showed a substantial decrease when animals age. At the same time, however, such a decrease was not observed when hypertension developed in the SHR. In contrast, Neuropeptide FF (NPFF) and Prolactin Releasing Peptide (PrRP) expression in the PNS associated Nucleus Tractus Solitarius (NTS) and Dorsal Motor Nucleus of the Vagus (DMV) diminished substantially, not only after the establishment of hypertension but also before its onset. Therefore, the current results indicate early changes in areas of the central nervous system involved in SNS and PNS control of blood pressure and associated with the development of hypertension.
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Affiliation(s)
- Ajda Yilmaz
- Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam 1105 BA, the Netherlands
| | - Andries Kalsbeek
- Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam 1105 BA, the Netherlands; Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands
| | - Ruud M Buijs
- Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam 1105 BA, the Netherlands; Department of Cell Biology and Physiology, Institute for Biomedical Research, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico.
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18
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Torino C, Tripepi R, Versace MC, Vilasi A, Tripepi G, Panuccio V. Clinical Epidemiology of Systolic and Diastolic Orthostatic Hypotension in Patients on Peritoneal Dialysis. J Clin Med 2021; 10:3075. [PMID: 34300240 PMCID: PMC8304693 DOI: 10.3390/jcm10143075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/29/2021] [Accepted: 07/08/2021] [Indexed: 11/17/2022] Open
Abstract
Blood pressure changes upon standing reflect a hemodynamic response, which depends on the baroreflex system and euvolemia. Dysautonomia and fluctuations in blood volume are hallmarks in kidney failure requiring replacement therapy. Orthostatic hypotension has been associated with mortality in hemodialysis patients, but neither this relationship nor the impact of changes in blood pressure has been tested in patients on peritoneal dialysis. We investigated both these relationships in a cohort of 137 PD patients. The response to orthostasis was assessed according to a standardized protocol. Twenty-five patients (18%) had systolic orthostatic hypotension, and 17 patients (12%) had diastolic hypotension. The magnitude of systolic and diastolic BP changes was inversely related to the value of the corresponding supine BP component (r = -0.16, p = 0.056 (systolic) and r = -0.25, p = 0.003 (diastolic), respectively). Orthostatic changes in diastolic, but not in systolic, BP were linearly related to the death risk (HR (1 mmHg reduction): 1.04, 95% CI 1.01-1.07, p = 0.006), and this was also true for CV death (HR: 1.08, 95% CI 1.03-1.12, p = 0.001). The strength of this association was not affected by further data adjustment (p ≤ 0.05). These findings suggest that independent of the formal diagnosis of orthostatic hypotension, even minor orthostatic reductions in diastolic BP bear an excess death risk in this population.
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Affiliation(s)
- Claudia Torino
- National Research Council—Institute of Clinical Physiology, Via Vallone Petrara snc, 89124 Reggio Calabria, Italy; (C.T.); (R.T.); (M.C.V.); (A.V.); (G.T.)
| | - Rocco Tripepi
- National Research Council—Institute of Clinical Physiology, Via Vallone Petrara snc, 89124 Reggio Calabria, Italy; (C.T.); (R.T.); (M.C.V.); (A.V.); (G.T.)
| | - Maria Carmela Versace
- National Research Council—Institute of Clinical Physiology, Via Vallone Petrara snc, 89124 Reggio Calabria, Italy; (C.T.); (R.T.); (M.C.V.); (A.V.); (G.T.)
| | - Antonio Vilasi
- National Research Council—Institute of Clinical Physiology, Via Vallone Petrara snc, 89124 Reggio Calabria, Italy; (C.T.); (R.T.); (M.C.V.); (A.V.); (G.T.)
| | - Giovanni Tripepi
- National Research Council—Institute of Clinical Physiology, Via Vallone Petrara snc, 89124 Reggio Calabria, Italy; (C.T.); (R.T.); (M.C.V.); (A.V.); (G.T.)
| | - Vincenzo Panuccio
- Nephology, Dialysis and Transplantation Unit—GOM “Bianchi-Melacrino-Morelli”, Via Vallone Petrara snc, 89124 Reggio Calabria, Italy
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19
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Walther LM, von Känel R, Heimgartner N, Zuccarella-Hackl C, Ehlert U, Wirtz PH. Altered Cardiovascular Reactivity to and Recovery from Cold Face Test-Induced Parasympathetic Stimulation in Essential Hypertension. J Clin Med 2021; 10:2714. [PMID: 34205387 PMCID: PMC8235104 DOI: 10.3390/jcm10122714] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/11/2021] [Accepted: 06/14/2021] [Indexed: 12/15/2022] Open
Abstract
Essential hypertension is associated with increased sympathetic and diminished parasympathetic activity as well as impaired reactivity to sympathetic stimulation. However, reactivity and recovery from parasympathetic stimulation in hypertension are unknown. We investigated reactivity and recovery to primarily parasympathetic stimulation by Cold Face Test (CFT) in essential hypertension. Moreover, we tested whether chronic stress modulates CFT-reactivity dependent on hypertension status. The CFT was conducted by applying a cold face-mask for 2 min in 24 unmedicated, otherwise healthy hypertensive men and in 24 normotensive controls. Systolic and diastolic blood pressure (BP) and heart rate (HR) were measured repeatedly. Chronic stress was assessed with the Trier-Inventory-for-Chronic-Stress-Screening-Scale. Hypertensives did not exhibit diastolic BP decreases after CFT-cessation (p = 0.59) as did normotensives (p = 0.002) and failed to show HR decreases in immediate response to CFT (p = 0.62) when compared to normotensives (p < 0.001). Systolic BP reactivity and recovery patterns did not differ between hypertensives and normotensives (p = 0.44). Chronic stress moderated HR (p = 0.045) but not BP CFT-reactivity (p's > 0.64) with chronically stressed normotensives showing similar HR reactivity as hypertensives. Our findings indicate impaired diastolic BP and HR reactivity to and recovery from CFT in hypertensives and a moderating effect of chronic stress on HR reactivity potentially reflecting reduced relaxation ability of the cardiovascular system.
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Affiliation(s)
- Lisa-Marie Walther
- Biological Work and Health Psychology, University of Konstanz, 78457 Konstanz, Germany;
- Centre for the Advanced Study of Collective Behaviour, University of Konstanz, 78457 Konstanz, Germany
| | - Roland von Känel
- Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (R.v.K.); (C.Z.-H.)
| | - Nadja Heimgartner
- Division of Clinical Psychology and Psychotherapy, University of Basel, 4055 Basel, Switzerland;
| | - Claudia Zuccarella-Hackl
- Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (R.v.K.); (C.Z.-H.)
| | - Ulrike Ehlert
- Department of Clinical Psychology and Psychotherapy, University of Zurich, 8050 Zurich, Switzerland;
| | - Petra H. Wirtz
- Biological Work and Health Psychology, University of Konstanz, 78457 Konstanz, Germany;
- Centre for the Advanced Study of Collective Behaviour, University of Konstanz, 78457 Konstanz, Germany
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20
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Cremer A, Boutouyrie P, Laurent S, Gosse P, Tzourio C. Orthostatic hypotension: a marker of blood pressure variability and arterial stiffness: a cross-sectional study on an elderly population: the 3-City study. J Hypertens 2021; 38:1103-1109. [PMID: 32371800 DOI: 10.1097/hjh.0000000000002374] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
BACKGROUND Orthostatic hypotension, blood pressure (BP) variability, and arterial stiffness are three markers of cardiovascular risk beyond the average BP. However, the relationships between these three parameters are not well known. AIM To examine the relationships between orthostatic hypotension, BP variability, and arterial stiffness. METHODS AND RESULTS In the Three-City study, a sample of 1151 elderly participants (mean age = 80 ± 3 years) was screened for orthostatic hypotension, undertook home BP and pulse wave velocity (PWV) measurements. We performed logistic regression analyses to look at the associations between orthostatic hypotension and both day-to-day (D-to-D) BP variability quartiles and PWV quartiles. Orthostatic hypotension was detected in 210 participants who were more likely to be hypertensive, exhibit higher BP variability and have increased arterial stiffness. In the multivariate logistic regression analysis, the frequency of orthostatic hypotension increased by 20% with every quartile of D-to-D SBP variability and by 20% with every quartile of PWV. PWV and D-to-D BP variability were not associated. In stratified analysis, the use of beta-blocker changes these relationships: orthostatic hypotension was not associated to PWV anymore but its association with D-to-D SBP variability was apparently stronger. CONCLUSION In this large sample of elderly individuals, orthostatic hypotension was independently associated with both BP variability and PWV. BP variability being more indicative of a baroreflex dysfunction and PWV being a marker of vascular ageing, these two components would participate to the orthostatic hypotension mechanisms.
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Affiliation(s)
- Antoine Cremer
- Department of Cardiology and Hypertension, Bordeaux University Hospital.,University Bordeaux, Inserm, Bordeaux Population HealthResearch Center, UMR 1219.,CHU de Bordeaux, Pole de sante publique, Service d'information medicale, Bordeaux
| | - Pierre Boutouyrie
- Université Paris Descartes Sorbonne Paris-Cité.,Assistance Publique Hôpitaux de Paris, Hôpital Georges Pompidou.,Institut National de la Santé et de la Recherche Médicale U 970, Paris, France
| | - Stéphane Laurent
- Université Paris Descartes Sorbonne Paris-Cité.,Assistance Publique Hôpitaux de Paris, Hôpital Georges Pompidou.,Institut National de la Santé et de la Recherche Médicale U 970, Paris, France
| | - Philippe Gosse
- Department of Cardiology and Hypertension, Bordeaux University Hospital
| | - Christophe Tzourio
- University Bordeaux, Inserm, Bordeaux Population HealthResearch Center, UMR 1219.,CHU de Bordeaux, Pole de sante publique, Service d'information medicale, Bordeaux
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21
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Pribék IK, Szűcs KF, Süle M, Grosz G, Ducza E, Vigh D, Tóth E, Janka Z, Kálmán J, Datki ZL, Gáspár R, Andó B. Detection of acute stress by smooth muscle electromyography: A translational study on rat and human. Life Sci 2021; 277:119492. [PMID: 33864819 DOI: 10.1016/j.lfs.2021.119492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 03/22/2021] [Accepted: 04/03/2021] [Indexed: 11/28/2022]
Abstract
AIMS Non-invasive and simultaneous recording of gastrointestinal (GI) activity during stress induction is still an unexplored field. In our previous investigation, the stress-induced alteration of the gastrointestinal tract was explored in rats. Our aims were to expand our previous rat experiment and to induce stress response in rats (Study 1) and humans (Study 2) to detect the GI tract activity, heart rate and body temperature. MATERIALS AND METHODS In the preclinical sample, acute stress was induced by immobilization in Sprague-Dawley rats (N = 10). Acute stress response was generated by the Trier Social Stress Test among healthy volunteers (N = 16). Detection of acute stress was measured by using smooth muscle electromyography, which recorded the myoelectric waves of the gastrointestinal tract (stomach, ileum and colon) simultaneously with heart rate and body temperature in rats and humans. KEY FINDINGS The myoelectric waves of the stomach, the cecum and the ileum increased during immobilization in rats, rising in parallel with heart rate and the dermal temperature of the abdominal surface. The same alterations were found during the stress period among humans, except in the case of the colon, where no change was detected. SIGNIFICANCE The crucial role of the GI tract in stress response was revealed by translating the outcome of basic research into human results. The similar GI alterations during stress in rats and humans underpin the robustness of our findings. In summary, our preliminary translational-based study can serve as an appropriate basis for further human studies.
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Affiliation(s)
- Ildikó Katalin Pribék
- Department of Psychiatry, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - Kálmán Ferenc Szűcs
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | | | | | - Eszter Ducza
- Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
| | - Dóra Vigh
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - Erika Tóth
- Department of Psychiatry, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - Zoltán Janka
- Department of Psychiatry, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - János Kálmán
- Department of Psychiatry, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - Zsolt László Datki
- Department of Psychiatry, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - Róbert Gáspár
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
| | - Bálint Andó
- Department of Psychiatry, Faculty of Medicine, University of Szeged, Szeged, Hungary.
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22
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Ghiasi S, Greco A, Faes L, Javorka M, Barbieri R, Scilingo EP, Valenza G. Quantifying multidimensional control mechanisms of cardiovascular dynamics during multiple concurrent stressors. Med Biol Eng Comput 2021; 59:775-785. [PMID: 33665768 DOI: 10.1007/s11517-020-02311-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 12/30/2020] [Indexed: 10/22/2022]
Abstract
Heartbeat regulation is achieved through different routes originating from central autonomic network sources, as well as peripheral control mechanisms. While previous studies successfully characterized cardiovascular regulatory mechanisms during a single stressor, to the best of our knowledge, a combination of multiple concurrent elicitations leading to the activation of different autonomic regulatory routes has not been investigated yet. Therefore, in this study, we propose a novel modeling framework for the quantification of heartbeat regulatory mechanisms driven by different neural routes. The framework is evaluated using two heartbeat datasets gathered from healthy subjects undergoing physical and mental stressors, as well as their concurrent administration. Experimental results indicate that more than 70% of the heartbeat regulatory dynamics is driven by the physical stressor when combining physical and cognitive/emotional stressors. The proposed framework provides quantitative insights and novel perspectives for neural activity on cardiac control dynamics, likely highlighting new biomarkers in the psychophysiology and physiopathology fields. A Matlab implementation of the proposed tool is available online.
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Affiliation(s)
- Shadi Ghiasi
- Department of Information Engineering & Research Center E. Piaggio, University of Pisa, Pisa, Italy.
| | - Alberto Greco
- Department of Information Engineering & Research Center E. Piaggio, University of Pisa, Pisa, Italy
| | - Luca Faes
- Department of Engineering, University of Palermo, Palermo, Italy
| | - Michal Javorka
- Department of Physiology and the Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
| | - Riccardo Barbieri
- Department of Electronics, Informatics and Bioengineering, Politecnico di Milano, Milano, Italy
| | - Enzo Pasquale Scilingo
- Department of Information Engineering & Research Center E. Piaggio, University of Pisa, Pisa, Italy
| | - Gaetano Valenza
- Department of Information Engineering & Research Center E. Piaggio, University of Pisa, Pisa, Italy
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23
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Jiang X, Guo Y, Zhao Y, Gao X, Peng D, Zhang H, Deng W, Fu W, Qin N, Chang R, Manor B, Lipsitz LA, Zhou J. Multiscale Dynamics of Blood Pressure Fluctuation Is Associated With White Matter Lesion Burden in Older Adults With and Without Hypertension: Observations From a Pilot Study. Front Cardiovasc Med 2021; 8:636702. [PMID: 33718456 PMCID: PMC7952298 DOI: 10.3389/fcvm.2021.636702] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 01/25/2021] [Indexed: 01/17/2023] Open
Abstract
Background: White matter lesions (WMLs) are highly prevalent in older adults, and hypertension is one of the main contributors to WMLs. The blood pressure (BP) is regulated by complex underlying mechanisms over multiple time scales, thus the continuous beat-to-beat BP fluctuation is complex. The association between WMLs and hypertension may be manifested as diminished complexity of BP fluctuations. The aim of this pilot study is to explore the relationships between hypertension, BP complexity, and WMLs in older adults. Method: Fifty-three older adults with clinically diagnosed hypertension and 47 age-matched older adults without hypertension completed one MRI scan and one BP recording of 10-15 min when sitting quietly. Their cerebral WMLs were assessed by two neurologists using the Fazekas scale based on brain structural MRI of each of their own. Greater score reflected higher WML grade. The complexity of continuous systolic (SBP) and diastolic (DBP) BP series was quantified using multiscale entropy (MSE). Lower MSE reflected lower complexity. Results: Compared to the non-hypertensive group, hypertensives had significantly greater Fazekas scores (F > 5.3, p < 0.02) and lower SBP and DBP complexity (F > 8.6, p < 0.004). Both within each group (β < -0.42, p < 0.01) and across groups (β < -0.47, p < 0.003), those with lower BP complexity had higher Fazekas score. Moreover, complexity of both SBP and DBP mediated the influence of hypertension on WMLs (indirect effects > 0.25, 95% confidence intervals = 0.06 - 0.50). Conclusion: These results suggest that diminished BP complexity is associated with WMLs and may mediate the influence of hypertension on WMLs. Future longitudinal studies are needed to examine the causal relationship between BP complexity and WMLs.
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Affiliation(s)
- Xin Jiang
- Department of Geriatrics, Shenzhen People's Hospital, Shenzhen, China.,The Second Clinical Medical College, Jinan University, Shenzhen, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China
| | - Yi Guo
- The Second Clinical Medical College, Jinan University, Shenzhen, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China.,Department of Neurology, Shenzhen People's Hospital, Shenzhen, China.,Shenzhen Bay Laboratory, Shenzhen, China
| | - Yue Zhao
- Department of Electrical and Computer Engineering, University of Rochester, Rochester, NY, United States
| | - Xia Gao
- Department of Geriatrics, Shenzhen People's Hospital, Shenzhen, China.,The Second Clinical Medical College, Jinan University, Shenzhen, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China
| | - Dan Peng
- Department of Geriatrics, Shenzhen People's Hospital, Shenzhen, China.,The Second Clinical Medical College, Jinan University, Shenzhen, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China
| | - Hui Zhang
- The Second Clinical Medical College, Jinan University, Shenzhen, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China.,Department of Neurology, Shenzhen People's Hospital, Shenzhen, China
| | - Wuhong Deng
- Department of Geriatrics, Shenzhen People's Hospital, Shenzhen, China.,The Second Clinical Medical College, Jinan University, Shenzhen, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China
| | - Wen Fu
- Department of Geriatrics, Shenzhen People's Hospital, Shenzhen, China.,The Second Clinical Medical College, Jinan University, Shenzhen, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China
| | - Na Qin
- Department of Geriatrics, Shenzhen People's Hospital, Shenzhen, China.,The Second Clinical Medical College, Jinan University, Shenzhen, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China
| | - Ruizhen Chang
- Department of Geriatrics, Shenzhen People's Hospital, Shenzhen, China.,The Second Clinical Medical College, Jinan University, Shenzhen, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China
| | - Brad Manor
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, United States.,Division of Gerontology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States
| | - Lewis A Lipsitz
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, United States.,Division of Gerontology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States
| | - Junhong Zhou
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, United States.,Division of Gerontology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States
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24
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Meusel M, Herrmann M, Machleidt F, Franzen K, Vonthein R, Sayk F. Intranasal oxytocin has sympathoexcitatory effects on vascular tone in healthy males. Am J Physiol Regul Integr Comp Physiol 2020; 320:R162-R172. [PMID: 33296278 DOI: 10.1152/ajpregu.00062.2020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Oxytocin appears to be involved in the neuroendocrine regulation of sympathetic blood pressure (BP) homeostasis. In animals, intracerebral administration of oxytocin induces BP-relevant sympathetic activation. In humans, central nervous effects of oxytocin on BP regulation remain unclear. Intranasal administration supposedly delivers oligopeptides such as oxytocin directly to the brain. We investigated the effects of intranasal oxytocin on sympathetic vascular baroreflex function in humans using microneurographic techniques. In a balanced, double-blind crossover design, oxytocin or placebo was administered intranasally to 12 lean, healthy males (age 25 ± 4 yr). Muscle sympathetic nerve activity (MSNA) was assessed microneurographically before (presubstance), 30-45 min (postsubstance I), and 105-120 min (postsubstance II) after oxytocin administration. Baroreflex was challenged via graded infusions of vasoactive drugs, and correlation of BP with MSNA and heart rate (HR) defined baroreflex function. Experiments were conducted in the afternoon after a 5-h fasting period. After oxytocin, resting MSNA (burst rate and total activity) showed significant net increases from pre to postsubstance II compared with placebo [Δincrease = +4.3 ± 1.2 (oxytocin) vs. +2.2 ± 1.4 bursts/min (placebo), ANOVA; P < 0.05; total activity = 184 ± 11.5% (oxytocin) vs. 121 ± 14.3% (placebo), ANOVA; P = 0.01). This was combined with a small but significant net increase in resting diastolic BP, whereas systolic and mean arterial BP or HR as well as baroreflex sensitivity at vasoactive drug challenge were not altered. Intranasally administered oxytocin induced vasoconstrictory sympathoactivation in healthy male humans. The concomitant increase of diastolic BP was most likely attributable to increased vascular tone. This suggests oxytocin-mediated upward resetting of the vascular baroreflex set point at centers superordinate to the mere baroreflex-feedback loop.
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Affiliation(s)
- M Meusel
- Department of Internal Medicine II, University Heart Center Luebeck, University Hospital Schleswig-Holstein, Luebeck, Germany
| | - M Herrmann
- Department of Internal Medicine II, University Heart Center Luebeck, University Hospital Schleswig-Holstein, Luebeck, Germany
| | - F Machleidt
- Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Luebeck, Germany
| | - K Franzen
- Department of Internal Medicine III, University Hospital of Schleswig-Holstein, Luebeck, Germany
| | - R Vonthein
- Institute for Medical Biometry and Statistics, University of Luebeck, Luebeck, Germany
| | - F Sayk
- Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Luebeck, Germany
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25
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Impact of in vitro embryo culture and transfer on blood pressure regulation in the adolescent lamb. J Dev Orig Health Dis 2020; 12:731-737. [PMID: 33185521 DOI: 10.1017/s2040174420001014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Nutrition during the periconceptional period influences postnatal cardiovascular health. We determined whether in vitro embryo culture and transfer, which are manipulations of the nutritional environment during the periconceptional period, dysregulate postnatal blood pressure and blood pressure regulatory mechanisms. Embryos were either transferred to an intermediate recipient ewe (ET) or cultured in vitro in the absence (IVC) or presence of human serum (IVCHS) and a methyl donor (IVCHS+M) for 6 days. Basal blood pressure was recorded at 19-20 weeks after birth. Mean arterial pressure (MAP) and heart rate (HR) were measured before and after varying doses of phenylephrine (PE). mRNA expression of signaling molecules involved in blood pressure regulation was measured in the renal artery. Basal MAP did not differ between groups. Baroreflex sensitivity, set point, and upper plateau were also maintained in all groups after PE stimulation. Adrenergic receptors alpha-1A (αAR1A), alpha-1B (αAR1B), and angiotensin II receptor type 1 (AT1R) mRNA expression were not different from controls in the renal artery. These results suggest there is no programmed effect of ET or IVC on basal blood pressure or the baroreflex control mechanisms in adolescence, but future studies are required to determine the impact of ET and IVC on these mechanisms later in the life course when developmental programming effects may be unmasked by age.
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26
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Zahner MR, Beaumont E. Intermittent Fasting After Spinal Cord Injury Does Not Improve the Recovery of Baroreflex Regulation in the Rat. Front Physiol 2020; 11:865. [PMID: 32792982 PMCID: PMC7387690 DOI: 10.3389/fphys.2020.00865] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Accepted: 06/26/2020] [Indexed: 01/04/2023] Open
Abstract
Modest recovery of somatic function after incomplete spinal cord injury (SCI) has been widely demonstrated. Recently we have shown that spontaneous recovery of baroreflex regulation of sympathetic activity also occurs in rats. Dietary restriction in the form of every other day fasting (EODF) has been shown to have beneficial effects on the recovery of motor function after SCI in rats. The goal of this study was to determine if EODF augments the improvement of baroreflex regulation of sympathetic activity after chronic left thoracic (T8) surgical spinal hemisection. To determine this, we performed baroreflex tests on ad-lib fed or EODF rats 1 week or 7 weeks after left T8 spinal hemisection. One week after T8 left hemisection baroreflex testing revealed that gain of baroreflex responsiveness, as well as the ability to increase renal sympathetic nerve activity (RSNA) at low arterial pressure, was significantly impaired in the ad-lib fed but not the EODF rats compared with sham lesioned control rats. However, baroreflex tests performed 7 weeks after T8 left hemisection revealed the inability of both ad-lib and EODF rats to decrease RSNA at elevated arterial pressures. While there is evidence to suggest that EODF has beneficial effects on the recovery of motor function in rats, EODF did not significantly improve the recovery of baroreflex regulation of sympathetic activity.
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Affiliation(s)
- Matthew R. Zahner
- Department of Health Sciences, College of Public Health, East Tennessee State University, Johnson City, TN, United States
| | - Eric Beaumont
- Department of Biomedical Science, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States
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27
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Green AL, Paterson DJ. Using Deep Brain Stimulation to Unravel the Mysteries of Cardiorespiratory Control. Compr Physiol 2020; 10:1085-1104. [PMID: 32941690 DOI: 10.1002/cphy.c190039] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
This article charts the history of deep brain stimulation (DBS) as applied to alleviate a number of neurological disorders, while in parallel mapping the electrophysiological circuits involved in generating and integrating neural signals driving the cardiorespiratory system during exercise. With the advent of improved neuroimaging techniques, neurosurgeons can place small electrodes into deep brain structures with a high degree accuracy to treat a number of neurological disorders, such as movement impairment associated with Parkinson's disease and neuropathic pain. As well as stimulating discrete nuclei and monitoring autonomic outflow, local field potentials can also assess how the neurocircuitry responds to exercise. This technique has provided an opportunity to validate in humans putative circuits previously identified in animal models. The central autonomic network consists of multiple sites from the spinal cord to the cortex involved in autonomic control. Important areas exist at multiple evolutionary levels, which include the anterior cingulate cortex (telencephalon), hypothalamus (diencephalon), periaqueductal grey (midbrain), parabrachial nucleus and nucleus of the tractus solitaries (brainstem), and the intermediolateral column of the spinal cord. These areas receive afferent input from all over the body and provide a site for integration, resulting in a coordinated efferent autonomic (sympathetic and parasympathetic) response. In particular, emerging evidence from DBS studies have identified the basal ganglia as a major sub-cortical cognitive integrator of both higher center and peripheral afferent feedback. These circuits in the basal ganglia appear to be central in coupling movement to the cardiorespiratory motor program. © 2020 American Physiological Society. Compr Physiol 10:1085-1104, 2020.
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Affiliation(s)
- Alexander L Green
- Division of Medical Sciences, Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - David J Paterson
- Department of Physiology Anatomy and Genetics, University of Oxford, Oxford, UK
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28
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Bailey R, Mortimore G. Orthostatic hypotension: clinical review and case study. BRITISH JOURNAL OF NURSING (MARK ALLEN PUBLISHING) 2020; 29:506-511. [PMID: 32407222 DOI: 10.12968/bjon.2020.29.9.506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Transient loss of consciousness (TLOC) accounts for 3% of all attendance in emergency departments within the UK. More than 90% of TLOC presentations are due to epileptic seizures, psychogenic seizures or syncope. However, in England and Wales in 2002, it was estimated that 92 000 patients were incorrectly diagnosed with epilepsy, at an additional annual cost to the NHS of up to £189 million. This article will reflect on the case study of a 54-year-old female patient who presented with a possible TLOC, and had a background of long-term depression. Differential diagnoses will be discussed, but the article will focus on orthostatic hypotension. Being diagnosed with this condition is independently associated with an increased risk of all-cause mortality. Causes of orthostatic hypotension and the pathophysiology behind the condition will be discussed, highlighting the importance of obtaining an accurate clinical history. This is extremely pertinent if a patient collapses in an NHS setting and this is witnessed by nurses because they can contribute to the history of the type of collapse, to aid diagnosis and correct treatment. In addition, nurses have a valuable role to play in highlighting polypharmacy to doctors, and non-medical prescribers, as a contributing factor to orthostatic hypotension is polypharmacy. It is therefore important to accurately distinguish TLOC aetiology, not only to provide appropriate management, but to also identify patients at risk of morbidity/mortality related to underlying disease.
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Affiliation(s)
- Rachael Bailey
- Trainee Advanced Clinical Practitioner, Department of Health and Social Care, University of Derby
| | - Gerri Mortimore
- Lecturer in Advanced Practice, Department of Health and Social Care, University of Derby
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29
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Cardioinhibitory syncope: from pathophysiology to treatment—should we think on cardioneuroablation? J Interv Card Electrophysiol 2020; 59:441-461. [DOI: 10.1007/s10840-020-00758-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Accepted: 04/23/2020] [Indexed: 02/07/2023]
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Rondanina E, Bovendeerd PHM. Stimulus-effect relations for left ventricular growth obtained with a simple multi-scale model: the influence of hemodynamic feedback. Biomech Model Mechanobiol 2020; 19:2111-2126. [PMID: 32358671 PMCID: PMC7603455 DOI: 10.1007/s10237-020-01327-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Accepted: 04/10/2020] [Indexed: 01/29/2023]
Abstract
Cardiac growth is an important mechanism for the human body to respond to changes in blood flow demand. Being able to predict the development of chronic growth is clinically relevant, but so far models to predict growth have not reached consensus on the stimulus–effect relation. In a previously published study, we modeled cardiac and hemodynamic function through a lumped parameter approach. We evaluated cardiac growth in response to valve disease using various stimulus–effect relations and observed an unphysiological decline pump function. Here we extend that model with a model of hemodynamic feedback that maintains mean arterial pressure and cardiac output through adaptation of peripheral resistance and circulatory unstressed volume. With the combined model, we obtain stable growth and restoration of pump function for most growth laws. We conclude that a mixed combination of stress and strain stimuli to drive cardiac growth is most promising since it (1) reproduces clinical observations on cardiac growth well, (2) requires only a small, clinically realistic adaptation of the properties of the circulatory system and (3) is robust in the sense that results were fairly insensitive to the exact choice of the chosen mechanics loading measure. This finding may be used to guide the choice of growth laws in more complex finite element models of cardiac growth, suitable for predicting the response to spatially varying changes in tissue load. Eventually, the current model may form a basis for a tool to predict patient-specific growth in response to spatially homogeneous changes in tissue load, since it is computationally inexpensive.
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Affiliation(s)
- Emanuele Rondanina
- Technische Universiteit Eindhoven, PO Box 513, 5600 MB, Eindhoven, The Netherlands.
| | - Peter H M Bovendeerd
- Technische Universiteit Eindhoven, PO Box 513, 5600 MB, Eindhoven, The Netherlands
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31
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Amorim MR, de Deus JL, Pereira CA, da Silva LEV, Borges GS, Ferreira NS, Batalhão ME, Antunes-Rodrigues J, Carnio EC, Tostes RC, Branco LGS. Baroreceptor denervation reduces inflammatory status but worsens cardiovascular collapse during systemic inflammation. Sci Rep 2020; 10:6990. [PMID: 32332859 PMCID: PMC7181760 DOI: 10.1038/s41598-020-63949-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 04/08/2020] [Indexed: 02/07/2023] Open
Abstract
Beyond the regulation of cardiovascular function, baroreceptor afferents play polymodal roles in health and disease. Sepsis is a life-threatening condition characterized by systemic inflammation (SI) and hemodynamic dysfunction. We hypothesized that baroreceptor denervation worsens lipopolysaccharide (LPS) induced-hemodynamic collapse and SI in conscious rats. We combined: (a) hemodynamic and thermoregulatory recordings after LPS administration at a septic-like non-lethal dose (b) analysis of the cardiovascular complexity, (c) evaluation of vascular function in mesenteric resistance vessels, and (d) measurements of inflammatory cytokines (plasma and spleen). LPS-induced drop in blood pressure was higher in sino-aortic denervated (SAD) rats. LPS-induced hemodynamic collapse was associated with SAD-dependent autonomic disbalance. LPS-induced vascular dysfunction was not affected by SAD. Surprisingly, SAD blunted LPS-induced surges of plasma and spleen cytokines. These data indicate that baroreceptor afferents are key to alleviate LPS-induced hemodynamic collapse, affecting the autonomic control of cardiovascular function, without affecting resistance blood vessels. Moreover, baroreflex modulation of the LPS-induced SI and hemodynamic collapse are not dependent of each other given that baroreceptor denervation worsened hypotension and reduced SI.
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Affiliation(s)
- Mateus R Amorim
- Dental School of Ribeirão Preto, 14040-904, University of São Paulo, São Paulo, Brazil.
| | - Júnia L de Deus
- Dental School of Ribeirão Preto, 14040-904, University of São Paulo, São Paulo, Brazil
| | - Camila A Pereira
- Ribeirão Preto Medical School, 14049-900, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Luiz E V da Silva
- Ribeirão Preto Medical School, 14049-900, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Gabriela S Borges
- Ribeirão Preto Medical School, 14049-900, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Nathanne S Ferreira
- Ribeirão Preto Medical School, 14049-900, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Marcelo E Batalhão
- Nursing School of Ribeirão Preto, 14040-902, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - José Antunes-Rodrigues
- Ribeirão Preto Medical School, 14049-900, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Evelin C Carnio
- Nursing School of Ribeirão Preto, 14040-902, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Rita C Tostes
- Ribeirão Preto Medical School, 14049-900, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Luiz G S Branco
- Dental School of Ribeirão Preto, 14040-904, University of São Paulo, São Paulo, Brazil. .,Ribeirão Preto Medical School, 14049-900, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
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32
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Kontos A, Baumert M, Lushington K, Kennedy D, Kohler M, Cicua-Navarro D, Pamula Y, Martin J. The Inconsistent Nature of Heart Rate Variability During Sleep in Normal Children and Adolescents. Front Cardiovasc Med 2020; 7:19. [PMID: 32154268 PMCID: PMC7046589 DOI: 10.3389/fcvm.2020.00019] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 02/03/2020] [Indexed: 12/26/2022] Open
Abstract
Introduction: Cardiac function is modulated by multiple factors including exogenous (circadian rhythm) and endogenous (ultradian 90–110 min sleep cycle) factors. By evaluating heart rate variability (HRV) during sleep, we will better understand their influence on cardiac activity. The aim of this study was to evaluate HRV in the dark phase of the circadian rhythm during sleep in healthy children and adolescents. Methods: One 3 min segment of pre-sleep electrocardiography (EEG) and 3, 6 min segments of electrocardiography recorded during polysomnography from 75 healthy children and adolescents were sampled during progressive cycles of slow wave sleep (SWS1, SWS2, SWS3). Three, 3 min segments of rapid eye movement sleep (REM) were also assessed, with REM1 marked at the last REM period before awakening. Studies that recorded REM3 prior to SWS3 were used for assessment. HRV variables include the following time domain values: mean NN (average RR intervals over given time), SDNN (Standard Deviation of RR intervals), and RMSSD (root Mean Square of beat-to-beat Differences). Frequency domain values include: low frequency (LF), high frequency (HF), and LF:HF. Results: Mixed linear effects model analysis revealed a significant difference in time and frequency domain values between sleep cycles and stages. Mean NN was lowest (highest heart rate) during pre—sleep then significantly increased across SWS1-3. Mean NN in SWS1 was similar to all REM periods which was significantly lower than both SWS2 and SWS3. SDNN remained at pre-sleep levels until SWS3, and then significantly increased in REM1&2. There was a large drop in LF from pre-sleep to SWS1. As cycles progressed through the night, LF remains lower than awake but increases to awake like levels by REM2. RMSSD and HF were lowest in pre-sleep and increased significantly by SWS1 and remain high and stable across stages and cycles except during the REM3 period where RMSSD decreased. Conclusion: Our results demonstrate that there are considerable changes in the spectral analysis of cardiac function occurring during different sleep stages and between sleep cycles across the night. Hence, time of night and sleep stage need to be considered when reporting any HRV differences.
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Affiliation(s)
- Anna Kontos
- Department of Respiratory and Sleep Medicine, Women's and Children's Hospital, Adelaide, SA, Australia.,School of Paediatrics and Reproductive Health, Robinson's Research Institute, University of Adelaide, Adelaide, SA, Australia
| | - Mathias Baumert
- School of Paediatrics and Reproductive Health, Robinson's Research Institute, University of Adelaide, Adelaide, SA, Australia.,School of Electrical and Electronic Engineering, University of Adelaide, Adelaide, SA, Australia
| | - Kurt Lushington
- School of Psychology, Social Work and Social Policy, University of South Australia, Adelaide, SA, Australia
| | - Declan Kennedy
- Department of Respiratory and Sleep Medicine, Women's and Children's Hospital, Adelaide, SA, Australia.,School of Paediatrics and Reproductive Health, Robinson's Research Institute, University of Adelaide, Adelaide, SA, Australia
| | - Mark Kohler
- School of Psychology, University of Adelaide, Adelaide, SA, Australia
| | - Diana Cicua-Navarro
- School of Psychology, Social Work and Social Policy, University of South Australia, Adelaide, SA, Australia
| | - Yvonne Pamula
- Department of Respiratory and Sleep Medicine, Women's and Children's Hospital, Adelaide, SA, Australia
| | - James Martin
- Department of Respiratory and Sleep Medicine, Women's and Children's Hospital, Adelaide, SA, Australia.,School of Paediatrics and Reproductive Health, Robinson's Research Institute, University of Adelaide, Adelaide, SA, Australia
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Wu P, Vaseghi M. The autonomic nervous system and ventricular arrhythmias in myocardial infarction and heart failure. PACING AND CLINICAL ELECTROPHYSIOLOGY: PACE 2020; 43:172-180. [PMID: 31823401 DOI: 10.1111/pace.13856] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 11/25/2019] [Accepted: 12/05/2019] [Indexed: 12/20/2022]
Abstract
Ventricular arrhythmias (VA) can range in presentation from asymptomatic to cardiac arrest and sudden cardiac death (SCD). Sustained ventricular tachycardias/ventricular fibrillation (VT/VF) are a common cause of SCD in the setting of myocardial infarction (MI) and heart failure. A particularly arrhythmogenic cardiac syncytia in these conditions can be attributed to both sympathetic activation and parasympathetic dysfunction, while appropriate neuromodulation has the potential to reduce occurrence of VT/VF. In this review, we outline the components of the autonomic nervous system that play an important role in normal cardiac electrophysiology and function. In addition, we discuss changes that occur in the setting of cardiac disease including adverse neural remodeling and neurohormonal activation which significantly contribute to propensity for VT/VF. Finally, we review neuromodulation strategies to mitigate VT/VF which predominantly rely on increasing parasympathetic drive and blockade of sympathetic neurotransmission.
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Affiliation(s)
- Perry Wu
- UCLA Cardiac Arrhythmia Center and UCLA Neurocardiology Research Program of Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Marmar Vaseghi
- UCLA Cardiac Arrhythmia Center and UCLA Neurocardiology Research Program of Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California
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34
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Dalmasso C, Leachman JR, Osborn JL, Loria AS. Sensory signals mediating high blood pressure via sympathetic activation: role of adipose afferent reflex. Am J Physiol Regul Integr Comp Physiol 2019; 318:R379-R389. [PMID: 31868518 DOI: 10.1152/ajpregu.00079.2019] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Blood pressure regulation in health and disease involves a balance between afferent and efferent signals from multiple organs and tissues. Although there are numerous reviews focused on the role of sympathetic nerves in different models of hypertension, few have revised the contribution of afferent nerves innervating adipose tissue and their role in the development of obesity-induced hypertension. Both clinical and basic research support the beneficial effects of bilateral renal denervation in lowering blood pressure. However, recent studies revealed that afferent signals from adipose tissue, in an adipose-brain-peripheral pathway, could contribute to the increased sympathetic activation and blood pressure during obesity. This review focuses on the role of adipose tissue afferent reflexes and briefly describes a number of other afferent reflexes modulating blood pressure. A comprehensive understanding of how multiple afferent reflexes contribute to the pathophysiology of essential and/or obesity-induced hypertension may provide significant insights into improving antihypertensive therapeutic approaches.
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Affiliation(s)
- Carolina Dalmasso
- Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, Kentucky
| | - Jacqueline R Leachman
- Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, Kentucky
| | - Jeffrey L Osborn
- Department of Biology, College of Arts and Sciences, University of Kentucky, Lexington, Kentucky
| | - Analia S Loria
- Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, Kentucky
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35
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Butyric acid, a gut bacteria metabolite, lowers arterial blood pressure via colon-vagus nerve signaling and GPR41/43 receptors. Pflugers Arch 2019; 471:1441-1453. [PMID: 31728701 PMCID: PMC6882756 DOI: 10.1007/s00424-019-02322-y] [Citation(s) in RCA: 113] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 09/26/2019] [Accepted: 10/07/2019] [Indexed: 01/01/2023]
Abstract
Butyric acid (BA) is a short-chain fatty acid (SCFA) produced by gut bacteria in the colon. We hypothesized that colon-derived BA may affect hemodynamics. Arterial blood pressure (BP) and heart rate (HR) were recorded in anesthetized, male, 14-week-old Wistar rats. A vehicle, BA, or 3-hydroxybutyrate, an antagonist of SCFA receptors GPR41/43 (ANT) were administered intravenously (IV) or into the colon (IC). Reactivity of mesenteric (MA) and gracilis muscle (GMA) arteries was tested ex vivo. The concentration of BA in stools, urine, portal, and systemic blood was measured with liquid chromatography coupled with mass spectrometry. BA administered IV decreased BP with no significant effect on HR. The ANT reduced, whereas L-NAME, a nitric oxide synthase inhibitor, did not affect the hypotensive effect of BA. In comparison to BA administered intravenously, BA administered into the colon produced a significantly longer decrease in BP and a decrease in HR, which was associated with a 2–3-fold increase in BA colon content. Subphrenic vagotomy and IC pretreatment with the ANT significantly reduced the hypotensive effect. Ex vivo, BA dilated MA and GMA. In conclusion, an increase in the concentration of BA in the colon produces a significant hypotensive effect which depends on the afferent colonic vagus nerve signaling and GPR41/43 receptors. BA seems to be one of mediators between gut microbiota and the circulatory system.
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36
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Cardiovascular autonomic responses in patients with Parkinson disease to pedunculopontine deep brain stimulation. Clin Auton Res 2019; 29:615-624. [DOI: 10.1007/s10286-019-00634-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 08/22/2019] [Indexed: 11/26/2022]
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37
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Cunha Silva C, Fontes MAP. Cardiovascular reactivity to emotional stress: The hidden challenge for pets in the urbanized environment. Physiol Behav 2019; 207:151-158. [PMID: 31100295 DOI: 10.1016/j.physbeh.2019.05.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 05/06/2019] [Accepted: 05/11/2019] [Indexed: 01/16/2023]
Abstract
Emotional stress is currently considered an important risk factor for cardiovascular diseases. Experimental evidence clearly shows robust autonomic cardiovascular effects in animals exposed to stress stimuli. Considering the remarkable variability of stressors, the urban environment can pose a severe challenge to cardiovascular control. Interestingly, pet ownership is indicated as an efficient non-pharmacological therapy to attenuate stress effects that can reduce the risk of cardiovascular disease. However, the risk of cardiovascular diseases in pets themselves living in urban environment has not received attention it deserves. Here, we review the central mechanisms involved in the autonomic cardiovascular response to emotional stress. Next, we discuss experimental evidence showing the cardiovascular effects produced by emotional stressors in animals, aiming to establish a parallel with common urban stressors. Association of additional risk factors such as sedentarism, obesity and ambient temperature are also considered. Our aim is to identify and raise awareness of the risk of cardiovascular disease in pets exposed to quotidian emotional stressors present in the urban environment.
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Affiliation(s)
- Carina Cunha Silva
- Department of Physiology & Biophysics, Institute of Biological Sciences Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Marco Antônio Peliky Fontes
- Department of Physiology & Biophysics, Institute of Biological Sciences Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil.
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38
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Meusel M, Herrmann M, Machleidt F, Franzen KF, Krapalis AF, Sayk F. GHRH-mediated GH release is associated with sympathoactivation and baroreflex resetting: a microneurographic study in healthy humans. Am J Physiol Regul Integr Comp Physiol 2019; 317:R15-R24. [PMID: 31042402 DOI: 10.1152/ajpregu.00033.2018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Previous research suggested substantial interactions of growth hormone (GH) and sympathetic nervous activity. This cross talk can be presumed both during physiological (e.g., slow-wave sleep) and pathological conditions of GH release. However, microneurographic studies of muscle sympathetic nerve activity (MSNA) and assessment of baroreflex function during acute GH-releasing hormone (GHRH)-mediated GH release were not conducted so far. In a balanced, double-blind crossover design, GHRH or placebo (normal saline) were intravenously administered to 11 healthy male volunteers. MSNA was assessed microneurographically and correlated with blood pressure (BP) and heart rate (HR) at rest before (pre-) and 30-45 (post-I) and 105-120 min (post-II) after respective injections. Additionally, baroreflex function was assessed via graded infusion of vasoactive drugs. GHRH increased GH serum levels as intended. Resting MSNA showed significant net increases of both burst rate and total activity from pre- to post-I and post-II following GHRH injections compared with placebo (ANOVA for treatment and time, burst rate: P = 0.028; total activity: P = 0.045), whereas BP and HR were not altered. ANCOVA revealed that the dependent variable MSNA was not affected by the independent variables mean arterial BP (MAP) or HR (MAP: P = 0.006; HR: P = 0.003). Baroreflex sensitivity at baroreflex challenge was not altered. GHRH-mediated GH release is associated with a significant sympathoactivation at central nervous sites superordinate to the simple baroreflex feedback loop because GH induced a baroreflex resetting without altering baroreflex sensitivity.
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Affiliation(s)
- Moritz Meusel
- Department of Internal Medicine II, University Hospital Schleswig-Holstein, Luebeck, Germany
| | - Magdalena Herrmann
- Department of Internal Medicine II, University Hospital Schleswig-Holstein, Luebeck, Germany
| | - Felix Machleidt
- Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Luebeck, Germany
| | - Klaas F Franzen
- Department of Internal Medicine III, University Hospital of Schleswig-Holstein, Luebeck, Germany
| | - Alexander F Krapalis
- Department of Internal Medicine I, University Hospital of Schleswig-Holstein, Luebeck, Germany
| | - Friedhelm Sayk
- Department of Internal Medicine II, University Hospital Schleswig-Holstein, Luebeck, Germany.,Department of Intensive Care Medicine, Sana-Kliniken, Luebeck, Germany
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Amorim MR, de Deus JL, Cazuza RA, Mota CMD, da Silva LEV, Borges GS, Batalhão ME, Cárnio EC, Branco LGS. Neuroinflammation in the NTS is associated with changes in cardiovascular reflexes during systemic inflammation. J Neuroinflammation 2019; 16:125. [PMID: 31221164 PMCID: PMC6587275 DOI: 10.1186/s12974-019-1512-6] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 06/03/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Lipopolysaccharide (LPS)-induced systemic inflammation (SI) is associated with neuroinflammation in the brain, hypotension, tachycardia, and multiple organs dysfunctions. Considering that during SI these important cardiovascular and inflammatory changes take place, we measured the sensitivity of the cardiovascular reflexes baroreflex, chemoreflex, and Bezold-Jarisch that are key regulators of hemodynamic function. We also evaluated neuroinflammation in the nucleus tractus solitarius (NTS), the first synaptic station that integrates peripheral signals arising from the cardiovascular and inflammatory status. METHODS We combined cardiovascular recordings, immunofluorescence, and assays of inflammatory markers in male Wistar rats that receive iv administration of LPS (1.5 or 2.5 mg kg-1) to investigate putative interactions of the neuroinflammation in the NTS and in the anteroventral preoptic region of the hypothalamus (AVPO) with the short-term regulation of blood pressure and heart rate. RESULTS LPS induced hypotension, tachycardia, autonomic disbalance, hypothermia followed by fever, and reduction in spontaneous baroreflex gain. On the other hand, during SI, the bradycardic component of Bezold-Jarisch and chemoreflex activation was increased. These changes were associated with a higher number of activated microglia and interleukin (IL)-1β levels in the NTS. CONCLUSIONS The present data are consistent with the notion that during SI and neuroinflammation in the NTS, rats have a reduced baroreflex gain, combined with an enhancement of the bradycardic component of Bezold-Jarisch and chemoreflex despite the important cardiovascular impairments (hypotension and tachycardia). These changes in the cardiac component of Bezold-Jarisch and chemoreflex may be beneficial during SI and indicate that the improvement of theses reflexes responsiveness though specific nerve stimulations may be useful in the management of sepsis.
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Affiliation(s)
- Mateus R. Amorim
- Dental School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP 14040-904 Brazil
| | - Júnia L. de Deus
- Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP 14049-900 Brazil
| | - Rafael A. Cazuza
- School of Philosophy, Science and Literature of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP 14040-901 Brazil
| | - Clarissa M. D. Mota
- Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP 14049-900 Brazil
| | - Luiz E. V. da Silva
- Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP 14049-900 Brazil
| | - Gabriela S. Borges
- Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP 14049-900 Brazil
| | - Marcelo E. Batalhão
- Nursing School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP 14040-902 Brazil
| | - Evelin C. Cárnio
- Nursing School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP 14040-902 Brazil
| | - Luiz G. S. Branco
- Dental School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP 14040-904 Brazil
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40
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Lee SK, Park YS, Cha KJ. Recovery of signal loss adopting the residual bootstrap method in fetal heart rate dynamics. ACTA ACUST UNITED AC 2019; 64:157-161. [PMID: 29550788 DOI: 10.1515/bmt-2017-0203] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Accepted: 10/04/2017] [Indexed: 11/15/2022]
Abstract
Fetal heart rate (FHR) data obtained from a non-stress test (NST) can be presented in a type of time series, which is accompanied by signal loss due to physical and biological causes. To recover or estimate FHR data, which is subjected to a high rate of signal loss, time series models [second-order autoregressive (AR(2)), first-order autoregressive conditional heteroscedasticity (ARCH(1)) and empirical mode decomposition and vector autoregressive (EMD-VAR)] and the residual bootstrap method were applied. The ARCH(1) model with the residual bootstrap technique was the most accurate [root mean square error (RMSE), 2.065] as it reflects the nonlinearity of the FHR data [mean absolute error (MAE) for approximate entropy (ApEn), 0.081]. As a result, the goal of predicting fetal health and identifying a high-risk pregnancy could be achieved. These trials may be effectively used to save the time and cost of repeating the NST when the fetal diagnosis is impossible owing to a large amount of signal loss.
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Affiliation(s)
- Sun-Kyung Lee
- Research Institute for Natural Science, Hanyang University, Seoul, Republic of Korea
| | - Young-Sun Park
- Research Institute for Natural Science, Hanyang University, Seoul, Republic of Korea
- Department of Mathematics, College of Natural Sciences, Hanyang University, Seoul, Republic of Korea
| | - Kyung-Joon Cha
- Research Institute for Natural Science, Hanyang University, Seoul, Republic of Korea
- Department of Mathematics, College of Natural Sciences, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
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41
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Guimarães DD, Cruz JC, Carvalho-Galvão A, Zhuge Z, Marques SM, Naves LM, Persson AEG, Weitzberg E, Lundberg JO, Balarini CM, Pedrino GR, Braga VA, Carlström M. Dietary Nitrate Reduces Blood Pressure in Rats With Angiotensin II–Induced Hypertension via Mechanisms That Involve Reduction of Sympathetic Hyperactivity. Hypertension 2019; 73:839-848. [DOI: 10.1161/hypertensionaha.118.12425] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Drielle D. Guimarães
- From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (D.D.G., J.C.C., Z.Z., A.E.G.P., E.W., J.O.L., M.C.)
- Biotechnology Center (D.D.G., J.C.C., A.C.-G., C.M.B., V.A.B.), Federal University of Paraiba, Joao Pessoa, Brazil
| | - Josiane C. Cruz
- From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (D.D.G., J.C.C., Z.Z., A.E.G.P., E.W., J.O.L., M.C.)
- Biotechnology Center (D.D.G., J.C.C., A.C.-G., C.M.B., V.A.B.), Federal University of Paraiba, Joao Pessoa, Brazil
| | - Alynne Carvalho-Galvão
- Biotechnology Center (D.D.G., J.C.C., A.C.-G., C.M.B., V.A.B.), Federal University of Paraiba, Joao Pessoa, Brazil
| | - Zhengbing Zhuge
- From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (D.D.G., J.C.C., Z.Z., A.E.G.P., E.W., J.O.L., M.C.)
| | - Stefanne M. Marques
- Department of Physiological Sciences, Federal University of Goias, Goiania, Brazil (S.M.M., L.M.N., G.R.P.)
| | - Lara M. Naves
- Department of Physiological Sciences, Federal University of Goias, Goiania, Brazil (S.M.M., L.M.N., G.R.P.)
| | - A. Erik G. Persson
- From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (D.D.G., J.C.C., Z.Z., A.E.G.P., E.W., J.O.L., M.C.)
- Department of Medical Cell Biology, Uppsala University, Sweden (A.E.G.P.)
| | - Eddie Weitzberg
- From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (D.D.G., J.C.C., Z.Z., A.E.G.P., E.W., J.O.L., M.C.)
| | - Jon O. Lundberg
- From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (D.D.G., J.C.C., Z.Z., A.E.G.P., E.W., J.O.L., M.C.)
| | - Camille M. Balarini
- Biotechnology Center (D.D.G., J.C.C., A.C.-G., C.M.B., V.A.B.), Federal University of Paraiba, Joao Pessoa, Brazil
- Health Sciences Center (C.M.B.), Federal University of Paraiba, Joao Pessoa, Brazil
| | - Gustavo R. Pedrino
- Department of Physiological Sciences, Federal University of Goias, Goiania, Brazil (S.M.M., L.M.N., G.R.P.)
| | - Valdir A. Braga
- Biotechnology Center (D.D.G., J.C.C., A.C.-G., C.M.B., V.A.B.), Federal University of Paraiba, Joao Pessoa, Brazil
| | - Mattias Carlström
- From the Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (D.D.G., J.C.C., Z.Z., A.E.G.P., E.W., J.O.L., M.C.)
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Papaioannou TG, Fasoulis R, Toumpaniaris P, Tsioufis C, Dilaveris P, Soulis D, Koutsouris D, Tousoulis D. Assessment of arterial baroreflex sensitivity by different computational analyses of pressure wave signals alone. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2019; 172:25-34. [PMID: 30902125 DOI: 10.1016/j.cmpb.2019.02.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 01/28/2019] [Accepted: 02/01/2019] [Indexed: 06/09/2023]
Abstract
BACKGROUND AND OBJECTIVE Baroreflex sensitivity (BRS) is an important indicator of the functionality of the arterial baroreceptors, and its assessment may have major research and clinical implications. An important requirement for its quantification is the continuous recording of electrocardiography (ECG) signal, so as to extract the RR interval, in parallel with continuous beat-to-beat blood pressure recording. We aimed to accurately calculate the RR Interval from pressure wave recordings per se, namely, the Pulse Interval (PI) using various arterial pulse wave analysis algorithms and to evaluate the precision and accuracy of BRS values calculated with the PI compared to BRS values calculated with the RR Interval. METHODS We analyzed the open access data of the Eurobavar study, which contains a set of ECG and arterial blood pressure (BP) wave signals recorded at 11 European centers. Pressure waveforms were continuously recorded by the Finapres apparatus which uses a finger cuff. The cuff pressure around the finger is dynamically adjusted by a servo-system to equal intra-arterial pressure, thus allowing the continuous recording of beat-to-beat BP waves. RR Interval was calculated from the ECG, whereas, PI was extracted from the arterial pulse waveforms, using 4 different methods (minimum, maximum, maximum 1st derivative and intersecting tangents method). BRS values were estimated by time domain and frequency domain methods. In order to compare agreement, accuracy, precision, variability, and the association between the reference BRS using the RR Interval and the BRS values using PI, standard statistical methods (i.e. intraclass correlation coefficients, RMSE, regression analysis) and Bland-Altman methods were performed. RESULTS We found that analysis of pressure waves alone by frequency-based (i.e. spectral) methods, provides the most accurate results of BRS estimation compared to time-domain methods (ICC > 0.9, R > 0.9, RMSE > 0.8 ms/mmHg). Concerning the spectral method, any algorithm for PI calculation is sufficient, as all show excellent agreement with the respective RR-intervals determined by ECG time series. Only the intersecting tangents and the maximum 1st derivative methods for PI calculation produce the most accurate results in time domain BRS estimation. CONCLUSION BRS estimation by proper analysis of pressure wave signals alone is feasible and accurate. Further studies are needed to investigate the clinical validity and relevance of the different BRS estimations in diagnostic, prognostic and therapeutic levels.
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Affiliation(s)
- Theodore G Papaioannou
- First Department of Cardiology, Units of Biomedical Engineering (TGP, DS), Hypertension (KT), e-Cardiology (PD), Hippokration Hospital, Medical School, National and Kapodistrian University of Athens. 114 Vas. Sophias ave., Athens 11527, Greece.
| | - Romanos Fasoulis
- First Department of Cardiology, Units of Biomedical Engineering (TGP, DS), Hypertension (KT), e-Cardiology (PD), Hippokration Hospital, Medical School, National and Kapodistrian University of Athens. 114 Vas. Sophias ave., Athens 11527, Greece; Biomedical Engineering Laboratory, School of Electrical and Computer Engineering, National Technical University of Athens. 9, Iroon Polytechniou Str., Athens 15780, Greece
| | - Petros Toumpaniaris
- Biomedical Engineering Laboratory, School of Electrical and Computer Engineering, National Technical University of Athens. 9, Iroon Polytechniou Str., Athens 15780, Greece
| | - Constantinos Tsioufis
- First Department of Cardiology, Units of Biomedical Engineering (TGP, DS), Hypertension (KT), e-Cardiology (PD), Hippokration Hospital, Medical School, National and Kapodistrian University of Athens. 114 Vas. Sophias ave., Athens 11527, Greece
| | - Polychronis Dilaveris
- First Department of Cardiology, Units of Biomedical Engineering (TGP, DS), Hypertension (KT), e-Cardiology (PD), Hippokration Hospital, Medical School, National and Kapodistrian University of Athens. 114 Vas. Sophias ave., Athens 11527, Greece
| | - Dimitrios Soulis
- First Department of Cardiology, Units of Biomedical Engineering (TGP, DS), Hypertension (KT), e-Cardiology (PD), Hippokration Hospital, Medical School, National and Kapodistrian University of Athens. 114 Vas. Sophias ave., Athens 11527, Greece
| | - Dimitrios Koutsouris
- Biomedical Engineering Laboratory, School of Electrical and Computer Engineering, National Technical University of Athens. 9, Iroon Polytechniou Str., Athens 15780, Greece
| | - Dimitrios Tousoulis
- First Department of Cardiology, Units of Biomedical Engineering (TGP, DS), Hypertension (KT), e-Cardiology (PD), Hippokration Hospital, Medical School, National and Kapodistrian University of Athens. 114 Vas. Sophias ave., Athens 11527, Greece
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Gerlach DA, Manuel J, Hoff A, Kronsbein H, Hoffmann F, Heusser K, Ehmke H, Diedrich A, Jordan J, Tank J, Beissner F. Novel Approach to Elucidate Human Baroreflex Regulation at the Brainstem Level: Pharmacological Testing During fMRI. Front Neurosci 2019; 13:193. [PMID: 30890917 PMCID: PMC6411827 DOI: 10.3389/fnins.2019.00193] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Accepted: 02/19/2019] [Indexed: 11/13/2022] Open
Abstract
Introduction: Brainstem nuclei govern the arterial baroreflex, which is crucial for heart rate and blood pressure control. Yet, brainstem function is difficult to explore in living humans and is therefore mostly studied using animal models or postmortem human anatomy studies. We developed a methodology to identify brainstem nuclei involved in baroreflex cardiovascular control in humans by combining pharmacological baroreflex testing with functional magnetic resonance imaging. Materials and Methods: In 11 healthy men, we applied eight repeated intravenous phenylephrine bolus doses of 25 and 75 μg followed by a saline flush using a remote-controlled injector during multiband functional magnetic resonance imaging (fMRI) acquisition of the whole brain including the brainstem. Continuous finger arterial blood pressure, respiration, and electrocardiogram (ECG) were monitored. fMRI data were preprocessed with a brainstem-specific pipeline and analyzed with a general linear model (GLM) to identify brainstem nuclei involved in central integration of the baroreceptor input. Results: Phenylephrine elicited a pressor response followed by a baroreflex-mediated lengthening of the RR interval (25 μg: 197 ± 15 ms; 75 μg: 221 ± 33 ms). By combining fMRI responses during both phenylephrine doses, we identified significant signal changes in the nucleus tractus solitarii (t = 5.97), caudal ventrolateral medulla (t = 4.59), rostral ventrolateral medulla (t = 7.11), nucleus ambiguus (t = 5.6), nucleus raphe obscurus (t = 6.45), and several other brainstem nuclei [p < 0.0005 family-wise error (few)-corr.]. Conclusion: Pharmacological baroreflex testing during fMRI allows characterizing central baroreflex regulation at the level of the brainstem in humans. Baroreflex-mediated activation and deactivation patterns are consistent with previous investigations in animal models. The methodology has the potential to elucidate human physiology and mechanisms of autonomic cardiovascular disease.
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Affiliation(s)
- Darius A Gerlach
- Department of Cardiovascular Aerospace Medicine, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany
| | - Jorge Manuel
- Somatosensory and Autonomic Therapy Research, Institute for Neuroradiology, Hannover Medical School, Hanover, Germany
| | - Alex Hoff
- Department of Cardiovascular Aerospace Medicine, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany
| | - Hendrik Kronsbein
- Department of Cardiovascular Aerospace Medicine, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.,Institute of Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Fabian Hoffmann
- Department of Cardiovascular Aerospace Medicine, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.,Division of Cardiology, Angiology and Pneumology, Cologne Heart Center, University Hospital Cologne, Cologne, Germany
| | - Karsten Heusser
- Department of Cardiovascular Aerospace Medicine, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany
| | - Heimo Ehmke
- Institute of Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - André Diedrich
- Division of Clinical Pharmacology, Department of Medicine, Autonomic Dysfunction Service, Vanderbilt University, Nashville, TN, United States
| | - Jens Jordan
- Chair of Aerospace Medicine, Institute of Aerospace Medicine, German Aerospace Center (DLR), Helmholtz Association of German Research Centers, Cologne, Germany
| | - Jens Tank
- Department of Cardiovascular Aerospace Medicine, Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany
| | - Florian Beissner
- Somatosensory and Autonomic Therapy Research, Institute for Neuroradiology, Hannover Medical School, Hanover, Germany
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Kunzendorf S, Klotzsche F, Akbal M, Villringer A, Ohl S, Gaebler M. Active information sampling varies across the cardiac cycle. Psychophysiology 2019; 56:e13322. [PMID: 30620083 DOI: 10.1111/psyp.13322] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 10/19/2018] [Accepted: 11/18/2018] [Indexed: 12/01/2022]
Abstract
Perception and cognition oscillate with fluctuating bodily states. For example, visual processing has been shown to change with alternating cardiac phases. Here, we study the heartbeat's role for active information sampling-testing whether humans implicitly act upon their environment so that relevant signals appear during preferred cardiac phases. During the encoding period of a visual memory experiment, participants clicked through a set of emotional pictures to memorize them for a later recognition test. By self-paced key press, they actively prompted the onset of short (100 ms) presented pictures. Simultaneously recorded electrocardiograms allowed us to analyze the self-initiated picture onsets relative to the heartbeat. We find that self-initiated picture onsets vary across the cardiac cycle, showing an increase during cardiac systole, while memory performance was not affected by the heartbeat. We conclude that active information sampling integrates heart-related signals, thereby extending previous findings on the association between body-brain interactions and behavior.
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Affiliation(s)
- Stella Kunzendorf
- Charité-Universitätsmedizin Berlin, Berlin, Germany.,Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.,MindBrainBody Institute at Berlin School of Mind and Brain, Berlin, Germany
| | - Felix Klotzsche
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.,MindBrainBody Institute at Berlin School of Mind and Brain, Berlin, Germany
| | - Mert Akbal
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.,MindBrainBody Institute at Berlin School of Mind and Brain, Berlin, Germany
| | - Arno Villringer
- Charité-Universitätsmedizin Berlin, Berlin, Germany.,Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.,MindBrainBody Institute at Berlin School of Mind and Brain, Berlin, Germany.,Leipzig Research Centre for Civilization Diseases (LIFE), University Hospital Leipzig, Leipzig, Germany
| | - Sven Ohl
- Bernstein Center of Computational Neuroscience, Berlin, Germany.,Humboldt-Universität zu Berlin, Berlin, Germany
| | - Michael Gaebler
- Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.,MindBrainBody Institute at Berlin School of Mind and Brain, Berlin, Germany.,Leipzig Research Centre for Civilization Diseases (LIFE), University Hospital Leipzig, Leipzig, Germany
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Ufnal M, Nowinski A. Central Administration of H 2S Donors for Studying Cardiovascular Effects of H 2S in Rats. Methods Mol Biol 2019; 2007:167-172. [PMID: 31148113 DOI: 10.1007/978-1-4939-9528-8_12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Increasing evidence suggests that hydrogen sulfide (H2S) is involved in brain mechanisms regulating the functions of the circulatory system. This appears to be mediated by cardiovascular centers located in the central nervous system. This chapter describes techniques of acute and chronic infusions into the brain cardiovascular centers in rats. Rats may be implanted either acutely or chronically with a cannula inserted into a selected cardiovascular center according to the stereotaxic coordinates. The cannula allows for the administration of the investigated compounds into a selected cardiovascular center.
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Affiliation(s)
- Marcin Ufnal
- Laboratory of Centre for Preclinical Research, Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Warsaw, Poland.
| | - Artur Nowinski
- Laboratory of Centre for Preclinical Research, Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Warsaw, Poland
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Gillies MJ, Huang Y, Hyam JA, Aziz TZ, Green AL. Direct neurophysiological evidence for a role of the human anterior cingulate cortex in central command. Auton Neurosci 2019; 216:51-58. [PMID: 30262256 PMCID: PMC6314459 DOI: 10.1016/j.autneu.2018.09.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Revised: 08/10/2018] [Accepted: 09/14/2018] [Indexed: 12/27/2022]
Abstract
INTRODUCTION The role of the anterior cingulate cortex (ACC) is still controversial. The ACC has been implicated in such diverse functions as cognition, arousal and emotion in addition to motor and autonomic control. Therefore the ACC is the ideal candidate to orchestrate cardiovascular performance in anticipation of perceived skeletal activity. The aim of this experiment was to investigate whether the ACC forms part of the neural network of central command whereby cardiovascular performance is governed by a top-down mechanism. METHODS & RESULTS Direct local field potential (LFP) recordings were made using intraparenchymal electrodes in six human ACC's to measure changes in neuronal activity during performance of a motor task in which anticipation of exercise was uncoupled from skeletal activity itself. Parallel cardiovascular arousal was indexed by electrocardiographic changes in heart rate. During anticipation of exercise, ACC LFP power within the 25-60 Hz frequency band increased significantly by 21% compared to rest (from 62.7 μV2/Hz (±SE 4.94) to 76.0μV2/Hz (±SE 7.24); p = 0.004). This 25-60 Hz activity increase correlated with a simultaneous heart rate increase during anticipation (Pearson's r = 0.417, p = 0.016). CONCLUSIONS/SIGNIFICANCE We provide the first invasive electrophysiological evidence to support the role of the ACC in both motor preparation and the top-down control of cardiovascular function in exercise. This further implicates the ACC in the body's response to the outside world and its possible involvement in such extreme responses as emotional syncope and hyperventilation. In addition we describe the frequency at which the neuronal ACC populations perform these tasks in the human.
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Affiliation(s)
- Martin J Gillies
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Department of Neurosurgery, John Radcliffe Hospital, Oxford, UK.
| | - Yongzhi Huang
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Jonathan A Hyam
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Department of Neurosurgery, John Radcliffe Hospital, Oxford, UK
| | - Tipu Z Aziz
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Department of Neurosurgery, John Radcliffe Hospital, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - Alexander L Green
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Department of Neurosurgery, John Radcliffe Hospital, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
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Abstract
The autonomic nervous system has widespread innervation to nearly every organ system in the body. In order to understand the basics of autonomic function, knowledge of the neuroanatomy of the autonomic nervous system is necessary. Frequently considered to control the "fight or flight" and "rest and digest" functions, the autonomic nervous system has an intricate network of connections to finely tune the systemic response to nearly any situation. Although traditionally considered two discrete systems (sympathetic and parasympathetic), the enteric nervous system is now considered a third component of the autonomic nervous system. This chapter reviews the background of the neuroanatomical distribution of the autonomic nervous system in order to facilitate understanding the basics of autonomic function.
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Affiliation(s)
- Christopher H Gibbons
- Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
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48
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Guo F, Gao S, Xu L, Sun X, Zhang N, Gong Y, Luan X. Arcuate Nucleus Orexin-A Signaling Alleviates Cisplatin-Induced Nausea and Vomiting Through the Paraventricular Nucleus of the Hypothalamus in Rats. Front Physiol 2018; 9:1811. [PMID: 30618823 PMCID: PMC6304364 DOI: 10.3389/fphys.2018.01811] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Accepted: 12/04/2018] [Indexed: 01/06/2023] Open
Abstract
The most common side effects of cisplatin chemotherapy are nausea and vomiting, and the overwhelming majority of research studies on the mechanism of cisplatin-induced nausea have been focused on the “vomiting center.” As a modulatory center of gastric motility, the roles of the hypothalamus in nausea and vomiting remain unclear. In the present study, we investigated the effects of exogenous orexin-A injected into the arcuate nucleus (ARC) on cisplatin-induced nausea and vomiting, and the possible underlying mechanism. Kaolin intake was calculated daily in cisplatin-treated and saline-treated rats. Gastric motility recording, injections into the ARC, and lesions of the paraventricular nucleus (PVN) were used to study the effects of orexin-A and the hypothalamic nucleus on disorders of gastrointestinal function in cisplatin-treated rats. The pathway from the ARC to the PVN was observed through Fluoro-Gold retrograde tracing. Furthermore, an NPY Y1 receptor antagonist was administered to explore the possible mechanisms involved in the effects of orexin-A in the ARC. We illustrated that exogenous orexin-A injected into the ARC reduced kaolin intake and promoted gastric motility in cisplatin-treated rats, and these effects could have been blocked by an ipsilateral PVN lesion or co-injected antagonist of orexin-A-SB334867. Additional results showed that orexin-A-activated neurons in the ARC communicated directly with other neurons in the PVN that express neuropeptide Y (NPY). Furthermore, activation of the downstream NPY pathway was required for the observed effects of orexin in the ARC on cisplatin-induced nausea and vomiting. These findings reveal a novel neurobiological circuit from the ARC to the PVN that might provide a potential target for the prevention and treatment of cisplatin-induced nausea and vomiting.
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Affiliation(s)
- Feifei Guo
- Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Shengli Gao
- Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Luo Xu
- Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Xiangrong Sun
- Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, China
| | - Nana Zhang
- Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yanling Gong
- Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
| | - Xiao Luan
- Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, China
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Dampney RA, Michelini LC, Li DP, Pan HL. Regulation of sympathetic vasomotor activity by the hypothalamic paraventricular nucleus in normotensive and hypertensive states. Am J Physiol Heart Circ Physiol 2018; 315:H1200-H1214. [PMID: 30095973 PMCID: PMC6297824 DOI: 10.1152/ajpheart.00216.2018] [Citation(s) in RCA: 102] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 07/13/2018] [Accepted: 07/25/2018] [Indexed: 12/22/2022]
Abstract
The hypothalamic paraventricular nucleus (PVN) is a unique and important brain region involved in the control of cardiovascular, neuroendocrine, and other physiological functions pertinent to homeostasis. The PVN is a major source of excitatory drive to the spinal sympathetic outflow via both direct and indirect projections. In this review, we discuss the role of the PVN in the regulation of sympathetic output in normal physiological conditions and in hypertension. In normal healthy animals, the PVN presympathetic neurons do not appear to have a major role in sustaining resting sympathetic vasomotor activity or in regulating sympathetic responses to short-term homeostatic challenges such as acute hypotension or hypoxia. Their role is, however, much more significant during longer-term challenges, such as sustained water deprivation, chronic intermittent hypoxia, and pregnancy. The PVN also appears to have a major role in generating the increased sympathetic vasomotor activity that is characteristic of multiple forms of hypertension. Recent studies in the spontaneously hypertensive rat model have shown that impaired inhibitory and enhanced excitatory synaptic inputs to PVN presympathetic neurons are the basis for the heightened sympathetic outflow in hypertension. We discuss the molecular mechanisms underlying the presynaptic and postsynaptic alterations in GABAergic and glutamatergic inputs to PVN presympathetic neurons in hypertension. In addition, we discuss the ability of exercise training to correct sympathetic hyperactivity by restoring blood-brain barrier integrity, reducing angiotensin II availability, and decreasing oxidative stress and inflammation in the PVN.
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Affiliation(s)
- Roger A Dampney
- Department of Physiology, University of Sydney , Sydney, New South Wales , Australia
| | - Lisete C Michelini
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo , São Paulo , Brazil
| | - De-Pei Li
- Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center , Houston, Texas
| | - Hui-Lin Pan
- Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center , Houston, Texas
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50
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Upregulation of Nav1.6 expression in the rostral ventrolateral medulla of stress-induced hypertensive rats. Hypertens Res 2018; 41:1013-1022. [PMID: 30287879 DOI: 10.1038/s41440-018-0105-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Revised: 04/06/2018] [Accepted: 04/09/2018] [Indexed: 02/07/2023]
Abstract
The rostral ventrolateral medulla (RVLM) plays a key role in mediating the development of stress-induced hypertension (SIH) by excitation and/or inhibition of sympathetic preganglionic neurons. The voltage-gated sodium channel Nav1.6 has been found to contribute to neuronal hyperexcitability. To examine the expression of Nav1.6 in the RVLM during SIH, a rat model was established by administering electric foot-shocks and noises. We found that Nav1.6 protein expression in the RVLM of SIH rats was higher than that of control rats, peaking at the tenth day of stress. Furthermore, we observed changes in blood pressure correlating with days of stress, with systolic blood pressure (SBP) found to reach a similarly timed peak at the tenth day of stress. Percentages of cells exhibiting colocalization of Nav1.6 with NeuN, a molecular marker of neurons, indicated a strong correlation between upregulation of Nav1.6 expression in NeuN-positive cells and SBP. The level of RSNA was significantly increased after 10 days of stress induction than control group. Compared with the SIHR, knockdown of Nav1.6 in RVLM of the SIHR decreased the level of SBP, heart rate (HR) and renal sympathetic nerve activity (RSNA). These results suggest that upregulated Nav1.6 expression within neurons in the RVLM of SIH rats may contribute to overactivation of the sympathetic system in response to SIH development.
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