|
1
|
Szabó P, Bonet S, Hetényi R, Hanna D, Kovács Z, Prisztóka G, Križalkovičová Z, Szentpéteri J. Systematic review: pain, cognition, and cardioprotection-unpacking oxytocin's contributions in a sport context. Front Physiol 2024; 15:1393497. [PMID: 38915776 PMCID: PMC11194439 DOI: 10.3389/fphys.2024.1393497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 05/13/2024] [Indexed: 06/26/2024] Open
Abstract
Introduction This systematic review investigates the interplay between oxytocin and exercise; in terms of analgesic, anti-inflammatory, pro-regenerative, and cardioprotective effects. Furthermore, by analyzing measurement methods, we aim to improve measurement validity and reliability. Methods Utilizing PRISMA, GRADE, and MECIR protocols, we examined five databases with a modified SPIDER search. Including studies on healthy participants, published within the last 20 years, based on keywords "oxytocin," "exercise" and "measurement," 690 studies were retrieved initially (455 unique records). After excluding studies of clinically identifiable diseases, and unpublished and reproduction-focused studies, 175 studies qualified for the narrative cross-thematic and structural analysis. Results The analysis resulted in five categories showing the reciprocal impact of oxytocin and exercise: Exercise (50), Physiology (63), Environment (27), Social Context (65), and Stress (49). Exercise-induced oxytocin could promote tissue regeneration, with 32 studies showing its analgesic and anti-inflammatory effects, while 14 studies discussed memory and cognition. Furthermore, empathy-associated OXTR rs53576 polymorphism might influence team sports performance. Since dietary habits and substance abuse can impact oxytocin secretion too, combining self-report tests and repeated salivary measurements may help achieve precision. Discussion Oxytocin's effect on fear extinction and social cognition might generate strategies for mental training, and technical, and tactical development in sports. Exercise-induced oxytocin can affect the amount of stress experienced by athletes, and their response to it. However, oxytocin levels could depend on the type of sport in means of contact level, exercise intensity, and duration. The influence of oxytocin on athletes' performance and recovery could have been exploited due to its short half-life. Examining oxytocin's complex interactions with exercise paves the way for future research and application in sports science, psychology, and medical disciplines. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=512184, identifier CRD42024512184.
Collapse
Affiliation(s)
- Péter Szabó
- Faculty of Sciences, Institute of Sports Science and Physical Education, University of Pécs, Pécs, Hungary
- Faculty of Humanities, University of Pécs, Pécs, Hungary
- Medical School, Institute of Transdisciplinary Discoveries, University of Pécs, Pécs, Hungary
| | - Sara Bonet
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Roland Hetényi
- RoLink Biotechnology Kft., Pécs, Hungary
- Hungarian National Blood Transfusion Service, Budapest, Hungary
- Szentágothai Research Centre, University of Pécs, Pécs, Hungary
- National Virology Laboratory, University of Pécs, Pécs, Hungary
| | - Dániel Hanna
- RoLink Biotechnology Kft., Pécs, Hungary
- Hungarian National Blood Transfusion Service, Budapest, Hungary
- Szentágothai Research Centre, University of Pécs, Pécs, Hungary
- National Virology Laboratory, University of Pécs, Pécs, Hungary
| | - Zsófia Kovács
- Faculty of Sciences, Institute of Sports Science and Physical Education, University of Pécs, Pécs, Hungary
| | - Gyöngyvér Prisztóka
- Faculty of Sciences, Institute of Sports Science and Physical Education, University of Pécs, Pécs, Hungary
| | - Zuzana Križalkovičová
- Faculty of Health Sciences, Institute of Physiotherapy and Sport Science, Department of Sport Science, Pécs, Hungary
| | - József Szentpéteri
- Medical School, Institute of Transdisciplinary Discoveries, University of Pécs, Pécs, Hungary
| |
Collapse
|
|
2
|
Tsukamoto H, Olesen ND, Petersen LG, Suga T, Sørensen H, Nielsen HB, Ogoh S, Secher NH, Hashimoto T. Circulating Plasma Oxytocin Level Is Elevated by High-Intensity Interval Exercise in Men. Med Sci Sports Exerc 2024; 56:927-932. [PMID: 38115226 DOI: 10.1249/mss.0000000000003360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2023]
Abstract
PURPOSE We evaluated whether repeated high-intensity interval exercise (HIIE) influences plasma oxytocin (OT) concentration in healthy men, and, given that OT is mainly synthesized in the hypothalamus, we assessed the concentration difference between the arterial (OT ART ) versus the internal jugular venous OT concentration (OT IJV ). Additionally, we hypothesized that an increase in cerebral OT release and the circulating concentration would be augmented by repeated HIIE. METHODS Fourteen healthy men (age = 24 ± 2 yr; mean ± SD) performed two identical bouts of HIIE. These HIIE bouts included a warm-up at 50%-60% maximal workload ( Wmax ) for 5 min followed by four bouts of exercise at 80%-90% Wmax for 4 min interspersed by exercise at 50%-60% Wmax for 3 min. The HIIE bouts were separated by 60 min of rest. OT was evaluated in blood through radial artery and internal jugular vein catheterization. RESULTS Both HIIE bouts increased both OT ART (median [IQR], from 3.9 [3.4-5.4] to 5.3 [4.4-6.3] ng·mL -1 in the first HIIE, P < 0.01) and OT IJV (from 4.6 [3.4-4.8] to 5.9 [4.3-8.2] ng·mL -1 , P < 0.01), but OT ART-IJV was unaffected (from -0.24 [-1.16 to 1.08] to 0.04 [-0.88 to 0.78] ng·mL -1 , P = 1.00). The increased OT levels were similar in the first and second HIIE bouts (OT ARTP = 0.25, OT IJVP = 0.36). CONCLUSIONS Despite no change in the cerebral OT release via the internal jugular vein, circulating OT increases during HIIE regardless of the accumulated exercise volume, indicating that OT may play role as one of the exerkines.
Collapse
Affiliation(s)
| | | | | | - Tadashi Suga
- Institute of Advanced Research for Sport and Health Science, Ritsumeikan University, Shiga, JAPAN
| | - Henrik Sørensen
- Department of Anesthesia, Rigshospitalet, Department of Clinical Medicine, University of Copenhagen, Copenhagen, DENMARK
| | | | - Shigehiko Ogoh
- Department of Biomedical Engineering, Toyo University, Saitama, JAPAN
| | - Niels H Secher
- Department of Anesthesia, Rigshospitalet, Department of Clinical Medicine, University of Copenhagen, Copenhagen, DENMARK
| | | |
Collapse
|
|
3
|
Wang Y, Yu H, Shi Q, Xu M, Gao W. Spatiotemporal analysis of the effects of exercise on the hemodynamics of the aorta in hypertensive rats using fluid-structure interaction simulation. J Transl Int Med 2024; 12:64-77. [PMID: 39876983 PMCID: PMC11774211 DOI: 10.2478/jtim-2023-0140] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025] Open
Abstract
Background and Objective Hemodynamic changes that lead to increased blood pressure represent the main drivers of organ damage in hypertension. Prolonged increases to blood pressure can lead to vascular remodeling, which also affects vascular hemodynamics during the pathogenesis of hypertension. Exercise is beneficial for relieving hypertension, however the mechanistic link between exercise training and how it influences hemodynamics in the context of hypertension is not well understood. Methods n exercise model was developed using spontaneously hypertensive rats (SHR) subject to a 12-week treadmill training regime. The heart rates and blood pressures of rats were measured using the tail cuff method, while micro-computed tomography (CT) scanning was used to develop three-dimensional structures of rat aorta, and ultrasound was used to detect rat aortic blood flow and changes to vessel wall structures. Computational fluid dynamics (CFD) and fluid-structure interaction (FSI) models were used to simulate and measure hemodynamic parameters of the rat aortic vessels. In parallel, Masson staining was performed on fixed samples of blood vessels to investigate collagen volume fraction. Hypertensive rats in the sedentary and long-term exercise training groups were subjected to a single bout exercise training, and their aortic hemodynamic parameters were analyzed before, 5 min, 24 h, and 72 h after the single bout exercise. Results Of the two models, in comparison to actual ultrasonic measurement values recorded, we found that numerical simulation results from the FSI model could more accurately model blood flow in the ascending aorta of hypertensive rats, compared to the CFD model. Moreover, longterm exercise training improved local hemodynamic parameters of blood vessels, and led to improvements in adverse hemodynamic features documented, including time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT). Longterm exercise training of SHR also improved local vascular collagen deposition in the aorta, while improvements in vascular remodeling were also correlated with favorable hemodynamic parameters. Compared with sedentary SHR, signals for low TAWSS regions of the aortic arch in SHR on the long-term exercise regime shifted to the position of the ascending aorta after a single bout of exercise. Conclusions This study demonstrates that FSI is informative to study the spatiotemporal effects of long-term exercise training on hemodynamic changes within the aortas of hypertensive rats, and that long-term exercise is beneficial through its effects to modulate vascular hemodynamics in hypertension.
Collapse
Affiliation(s)
- Yueshen Wang
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing100191, China
| | - Haiyi Yu
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing100191, China
| | - Quanyou Shi
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing100191, China
| | - Ming Xu
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing100191, China
| | - Wei Gao
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing100191, China
| |
Collapse
|
|
4
|
Baumer-Harrison C, Breza JM, Sumners C, Krause EG, de Kloet AD. Sodium Intake and Disease: Another Relationship to Consider. Nutrients 2023; 15:535. [PMID: 36771242 PMCID: PMC9921152 DOI: 10.3390/nu15030535] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 01/14/2023] [Accepted: 01/15/2023] [Indexed: 01/22/2023] Open
Abstract
Sodium (Na+) is crucial for numerous homeostatic processes in the body and, consequentially, its levels are tightly regulated by multiple organ systems. Sodium is acquired from the diet, commonly in the form of NaCl (table salt), and substances that contain sodium taste salty and are innately palatable at concentrations that are advantageous to physiological homeostasis. The importance of sodium homeostasis is reflected by sodium appetite, an "all-hands-on-deck" response involving the brain, multiple peripheral organ systems, and endocrine factors, to increase sodium intake and replenish sodium levels in times of depletion. Visceral sensory information and endocrine signals are integrated by the brain to regulate sodium intake. Dysregulation of the systems involved can lead to sodium overconsumption, which numerous studies have considered causal for the development of diseases, such as hypertension. The purpose here is to consider the inverse-how disease impacts sodium intake, with a focus on stress-related and cardiometabolic diseases. Our proposition is that such diseases contribute to an increase in sodium intake, potentially eliciting a vicious cycle toward disease exacerbation. First, we describe the mechanism(s) that regulate each of these processes independently. Then, we highlight the points of overlap and integration of these processes. We propose that the analogous neural circuitry involved in regulating sodium intake and blood pressure, at least in part, underlies the reciprocal relationship between neural control of these functions. Finally, we conclude with a discussion on how stress-related and cardiometabolic diseases influence these circuitries to alter the consumption of sodium.
Collapse
Affiliation(s)
- Caitlin Baumer-Harrison
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32603, USA
- Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL 32610, USA
- Center for Smell and Taste, University of Florida, Gainesville, FL 32610, USA
- Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA
| | - Joseph M. Breza
- Department of Psychology, College of Arts and Sciences, Eastern Michigan University, Ypsilanti, MI 48197, USA
| | - Colin Sumners
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32603, USA
- Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL 32610, USA
- Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA
| | - Eric G. Krause
- Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL 32610, USA
- Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA
- Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA
| | - Annette D. de Kloet
- Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32603, USA
- Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL 32610, USA
- Center for Smell and Taste, University of Florida, Gainesville, FL 32610, USA
- Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA
| |
Collapse
|
|
5
|
Ludyga S, Ishihara T, Kamijo K. The Nervous System as a Pathway for Exercise to Improve Social Cognition. Exerc Sport Sci Rev 2022; 50:203-212. [PMID: 35749761 PMCID: PMC9470049 DOI: 10.1249/jes.0000000000000300] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
The promotion of autonomic balance and social brain networks may explain the association of endurance exercise and social cognition. Specific nervous system functions and the regulating roles of oxytocin have evolved because of the necessity to negotiate increasingly complex social systems. We hypothesize that acute and long-term physical activity and exercise have the potential to benefit social cognitive abilities, such as emotion recognition and regulation, by operating on these functions.
Collapse
Affiliation(s)
- Sebastian Ludyga
- Department of Sport, Exercise & Health, University of Basel, Switzerland
| | - Toru Ishihara
- Graduate School of Human Development and Environment, Kobe University, Japan
| | - Keita Kamijo
- Faculty of Liberal Arts and Sciences, Chukyo University, Japan
| |
Collapse
|
|
6
|
He FQ, Fan MY, Hui YN, Lai RJ, Chen X, Yang MJ, Cheng XX, Wang ZJ, Yu B, Yan BJ, Tian Z. Effects of treadmill exercise on anxiety-like behavior in association with changes in estrogen receptors ERα, ERβ and oxytocin of C57BL/6J female mice. IBRO Neurosci Rep 2021; 11:164-174. [PMID: 34746914 PMCID: PMC8551837 DOI: 10.1016/j.ibneur.2021.10.001] [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: 01/25/2021] [Accepted: 10/04/2021] [Indexed: 11/28/2022] Open
Abstract
Exercise can reduce the incidence of stress-related mental diseases, such as depression and anxiety. Control group was neither exposed to CVMS nor TRE (noCVMS/noTRE). Females were tested and levels of serum17-beta-oestradiol (E2), estrogen receptors α immunoreactive neurons (ERα-IRs), estrogen receptors β immunoreactive neurons (ERβ-IRs) and oxytocin immunoreactive neurons (OT-IRs) were measured. The results showed there's increased anxiety-like behaviors for mice from CVMS/noTRE, CVMS/higher speed TRE (CVMS/HTRE) and noCVMS/HTRE groups when they were put in open field and elevated maze tests. They had lower serum E2 levels than mice from CVMS/low-moderate speed TRE (CVMS/LMTRE), noCVMS/LMTRE and noCVMS/noTRE groups. The three groups of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice had more ERα-IRs and less ERβ-IRs in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST) and medial amygdala (MeA), hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The number of OT-IRs in PVN and SON of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice was also lower than that of mice from CVMS/LMTRE, noCVMS/LMTRE and noCVMS/noTRE groups. Interestingly, CVMS/LMTRE and noCVMS/LMTRE mice were similar to noCVMS/noTRE mice in that they did not show anxiety, while CVMS/HTRE and noCVMS/HTRE mice did not, which were similar to the mice in CVMS/noTRE. We propose that LMTRE instead of HTRE changes the serum concentration of E2. ERβ/ERα ratio and OT level in the brain may be responsible for the decrease in anxiety-like behavior in female mice exposed to anxiety-inducing stress conditions.
Collapse
Key Words
- BNST, bed nucleus of the stria terminalis
- CVMS, chronic variable moderate stress
- Chronic variable moderate stress (CVMS)
- E2, 17-beta-oestradiol
- ELISA, enzyme-linked immunosorbent assay
- EPM, elevated plusmazetest
- ERα-IRs, estrogen receptors αimmunoreactive neurons
- ERβ-IRs, estrogen receptor β immunoreactive neurons
- Estrogen receptor α (ERα)
- Estrogen receptor β (ERβ)
- HPA, hypothalamic–pituitary–adrenal
- HRP, horseradishperoxidase
- HTRE, higher speed TRE
- LMTRE, low-moderate speed TRE
- MeA, medial amygdaloid nucleus
- OF, open field test
- OT-IRs, Oxytocin immunoreactive neurons
- Oxytocin (OT)
- PBS, phosphatebufferedsolution
- PVN, paraventricular nucleus
- SON, supraoptic nucleus
- TRE, treadmill exercise
- Treadmill exercise (TRE)
- mPOA, medial preopticarea
Collapse
Affiliation(s)
- Feng-Qin He
- Key Laboratory of Natural Product Development and Anticancer Innovative Drug Research in Qinling, Xi'an 710065, China.,Genetic Engineering Laboratory, College of Biological and Environmental Engineering, Xi'an University, Xi'an 710065, China
| | - Mei-Yang Fan
- Key Laboratory of Natural Product Development and Anticancer Innovative Drug Research in Qinling, Xi'an 710065, China.,Genetic Engineering Laboratory, College of Biological and Environmental Engineering, Xi'an University, Xi'an 710065, China
| | - Yu-Nan Hui
- Key Laboratory of Natural Product Development and Anticancer Innovative Drug Research in Qinling, Xi'an 710065, China.,Genetic Engineering Laboratory, College of Biological and Environmental Engineering, Xi'an University, Xi'an 710065, China
| | - Rui-Juan Lai
- Key Laboratory of Natural Product Development and Anticancer Innovative Drug Research in Qinling, Xi'an 710065, China.,Genetic Engineering Laboratory, College of Biological and Environmental Engineering, Xi'an University, Xi'an 710065, China
| | - Xin Chen
- Key Laboratory of Natural Product Development and Anticancer Innovative Drug Research in Qinling, Xi'an 710065, China.,Genetic Engineering Laboratory, College of Biological and Environmental Engineering, Xi'an University, Xi'an 710065, China
| | - Ming-Juan Yang
- Key Laboratory of Natural Product Development and Anticancer Innovative Drug Research in Qinling, Xi'an 710065, China.,Genetic Engineering Laboratory, College of Biological and Environmental Engineering, Xi'an University, Xi'an 710065, China
| | - Xiao-Xia Cheng
- Key Laboratory of Natural Product Development and Anticancer Innovative Drug Research in Qinling, Xi'an 710065, China.,Genetic Engineering Laboratory, College of Biological and Environmental Engineering, Xi'an University, Xi'an 710065, China
| | - Zi-Jian Wang
- Key Laboratory of Natural Product Development and Anticancer Innovative Drug Research in Qinling, Xi'an 710065, China.,Genetic Engineering Laboratory, College of Biological and Environmental Engineering, Xi'an University, Xi'an 710065, China
| | - Bin Yu
- Key Laboratory of Natural Product Development and Anticancer Innovative Drug Research in Qinling, Xi'an 710065, China.,Genetic Engineering Laboratory, College of Biological and Environmental Engineering, Xi'an University, Xi'an 710065, China
| | - Bing-Jie Yan
- Key Laboratory of Natural Product Development and Anticancer Innovative Drug Research in Qinling, Xi'an 710065, China.,Genetic Engineering Laboratory, College of Biological and Environmental Engineering, Xi'an University, Xi'an 710065, China
| | - Zhen Tian
- Key Laboratory of Natural Product Development and Anticancer Innovative Drug Research in Qinling, Xi'an 710065, China.,Genetic Engineering Laboratory, College of Biological and Environmental Engineering, Xi'an University, Xi'an 710065, China
| |
Collapse
|
|
7
|
Szczepanska-Sadowska E, Wsol A, Cudnoch-Jedrzejewska A, Żera T. Complementary Role of Oxytocin and Vasopressin in Cardiovascular Regulation. Int J Mol Sci 2021; 22:11465. [PMID: 34768894 PMCID: PMC8584236 DOI: 10.3390/ijms222111465] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 10/21/2021] [Accepted: 10/22/2021] [Indexed: 12/17/2022] Open
Abstract
The neurons secreting oxytocin (OXY) and vasopressin (AVP) are located mainly in the supraoptic, paraventricular, and suprachiasmatic nucleus of the brain. Oxytocinergic and vasopressinergic projections reach several regions of the brain and the spinal cord. Both peptides are released from axons, soma, and dendrites and modulate the excitability of other neuroregulatory pathways. The synthesis and action of OXY and AVP in the peripheral organs (eye, heart, gastrointestinal system) is being investigated. The secretion of OXY and AVP is influenced by changes in body fluid osmolality, blood volume, blood pressure, hypoxia, and stress. Vasopressin interacts with three subtypes of receptors: V1aR, V1bR, and V2R whereas oxytocin activates its own OXTR and V1aR receptors. AVP and OXY receptors are present in several regions of the brain (cortex, hypothalamus, pons, medulla, and cerebellum) and in the peripheral organs (heart, lungs, carotid bodies, kidneys, adrenal glands, pancreas, gastrointestinal tract, ovaries, uterus, thymus). Hypertension, myocardial infarction, and coexisting factors, such as pain and stress, have a significant impact on the secretion of oxytocin and vasopressin and on the expression of their receptors. The inappropriate regulation of oxytocin and vasopressin secretion during ischemia, hypoxia/hypercapnia, inflammation, pain, and stress may play a significant role in the pathogenesis of cardiovascular diseases.
Collapse
Affiliation(s)
- Ewa Szczepanska-Sadowska
- Laboratory of Centre for Preclinical Research, Chair and Department of Experimental and Clinical Physiology, Medical University of Warsaw, 02-091 Warsaw, Poland; (A.W.); (A.C.-J.); (T.Ż.)
| | | | | | | |
Collapse
|
|
8
|
Inhibition of nNOS in the paraventricular nucleus of hypothalamus decreases exercise-induced hyperthermia. Brain Res Bull 2021; 177:64-72. [PMID: 34536522 DOI: 10.1016/j.brainresbull.2021.09.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 08/21/2021] [Accepted: 09/10/2021] [Indexed: 11/23/2022]
Abstract
The paraventricular nucleus of the hypothalamus (PVN) is an important site for autonomic control, which integrates thermoregulation centers and sympathetic outflow to thermoeffector organs. PVN neurons express the neuronal isoform of nitric oxide synthase (nNOS) whose expression is locally upregulated by physical exercise. Thus, the aim of the present study was to evaluate the role of nNOS in the PVN in the exercise-induced hyperthermia. Seven days after surgery, male Wistar rats received bilateral intra-PVN microinjections of the selective nNOS inhibitor Nw-Propyl-L-Arginine (NPLA) or vehicle (saline) and were submitted to an acute progressive exercise session on a treadmill until fatigue. Abdominal and tail skin temperature (Tabd and Ttail, respectively) were measured, and the threshold (Hthr; °C) and sensitivity (Hsen) for heat dissipation calculated. Performance variables were also collected. During the progressive exercise protocol, all animals displayed an increase in the Tabd. However, compared to vehicle group, the microinjection of NPLA in the PVN attenuated the exercise-induced hyperthermia. There was no difference in Ttail or Hthr between NPLA and control rats. In contrast, Hsen was increased in the NPLA group compared to vehicle. In addition, heat storage was lower in NPLA-treated animals. Despite the temperature differences, inhibition of nNOS in the PVN did not affect running performance on the treadmill. These results suggest that nitrergic signaling within the PVN, under nNOS activation, drives the increase of body temperature, being necessary for the proper thermal regulatory mechanisms during progressive exercise-induced hyperthermia.
Collapse
|
|
9
|
Aikins AO, Nguyen DH, Paundralingga O, Farmer GE, Shimoura CG, Brock C, Cunningham JT. Cardiovascular Neuroendocrinology: Emerging Role for Neurohypophyseal Hormones in Pathophysiology. Endocrinology 2021; 162:6247962. [PMID: 33891015 PMCID: PMC8234498 DOI: 10.1210/endocr/bqab082] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Indexed: 11/19/2022]
Abstract
Arginine vasopressin (AVP) and oxytocin (OXY) are released by magnocellular neurosecretory cells that project to the posterior pituitary. While AVP and OXY currently receive more attention for their contributions to affiliative behavior, this mini-review discusses their roles in cardiovascular function broadly defined to include indirect effects that influence cardiovascular function. The traditional view is that neither AVP nor OXY contributes to basal cardiovascular function, although some recent studies suggest that this position might be re-evaluated. More evidence indicates that adaptations and neuroplasticity of AVP and OXY neurons contribute to cardiovascular pathophysiology.
Collapse
Affiliation(s)
- Ato O Aikins
- Department of Physiology and Anatomy, Graduate School of Biomedical Sciences, UNT Health Science Center, Fort Worth, TX 76107, USA
| | - Dianna H Nguyen
- Department of Physiology and Anatomy, Graduate School of Biomedical Sciences, UNT Health Science Center, Fort Worth, TX 76107, USA
- Texas College of Osteopathic Medicine, UNT Health Science Center, Fort Worth, TX 76107, USA
| | - Obed Paundralingga
- Department of Physiology and Anatomy, Graduate School of Biomedical Sciences, UNT Health Science Center, Fort Worth, TX 76107, USA
| | - George E Farmer
- Department of Physiology and Anatomy, Graduate School of Biomedical Sciences, UNT Health Science Center, Fort Worth, TX 76107, USA
| | - Caroline Gusson Shimoura
- Department of Physiology and Anatomy, Graduate School of Biomedical Sciences, UNT Health Science Center, Fort Worth, TX 76107, USA
| | - Courtney Brock
- Department of Physiology and Anatomy, Graduate School of Biomedical Sciences, UNT Health Science Center, Fort Worth, TX 76107, USA
| | - J Thomas Cunningham
- Department of Physiology and Anatomy, Graduate School of Biomedical Sciences, UNT Health Science Center, Fort Worth, TX 76107, USA
- Correspondence: J. Thomas Cunningham Department of Physiology & Anatomy CBH 338 UNT Health Science Center 3500 Camp Bowie Blvd Fort Worth, TX 76107, USA.
| |
Collapse
|
|
10
|
Mohamed A, Alawna M. Enhancing oxygenation of patients with coronavirus disease 2019: Effects on immunity and other health-related conditions. World J Clin Cases 2021; 9:4939-4958. [PMID: 34307545 PMCID: PMC8283603 DOI: 10.12998/wjcc.v9.i19.4939] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 04/26/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) distresses the pulmonary system causing acute respiratory distress syndrome, which might lead to death. There is no cure for COVID-19 infection. COVID-19 is a self-limited infection, and the methods that can enhance immunity are strongly required. Enhancing oxygenation is one safe and effective intervention to enhance immunity and pulmonary functions. This review deliberates the probable influences of enhancing oxygenation on immunity and other health-connected conditions in patients with COVID-19. An extensive search was conducted through Web of Science, Scopus, Medline databases, and EBSCO for the influence of enhancing oxygenation on immunity, pulmonary functions, psycho-immune hormones, and COVID-19 risk factors. This search included clinical trials and literature and systematic reviews. This search revealed that enhancing oxygenation has a strong effect on improving immunity and pulmonary functions and psycho-immune hormones. Also, enhancing oxygenation has a self-protective role counter to COVID-19 risk factors. Lastly, this search revealed the recommended safe and effective exercise protocol to enhance oxygenation in patients with COVID-19. Enhancing oxygenation should be involved in managing patients with COVID-19 because of its significant effects on immunity, pulmonary functions, and COVID-19 risk factors. A mild to moderate cycling or walking with 60%-80% Vo2max for 20-60 min performed 2-3 times per week could be a safe and effective aerobic exercise program in patients with COVID-19 to enhance their immunity and pulmonary functions.
Collapse
Affiliation(s)
- Ayman Mohamed
- Department of Physiotherapy and Rehabilitation, Istanbul Gelisim University, Istanbul 34522, Turkey
- Department of Basic Science and Biomechanics, Faculty of Physical Therapy, Beni Suef University, Beni Suef 62521, Egypt
| | - Motaz Alawna
- Department of Physiotherapy and Rehabilitation, Istanbul Gelisim University, Istanbul 34522, Turkey
- Department of Physiotherapy and Rehabilitation, Faculty of Allied Medical Sciences, Arab American University, Jenin 24013, Palestine
| |
Collapse
|
|
11
|
Wallman-Jones A, Perakakis P, Tsakiris M, Schmidt M. Physical activity and interoceptive processing: Theoretical considerations for future research. Int J Psychophysiol 2021; 166:38-49. [PMID: 33965423 DOI: 10.1016/j.ijpsycho.2021.05.002] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 04/09/2021] [Accepted: 05/04/2021] [Indexed: 10/21/2022]
Abstract
Interoception, defined as the sense of the internal bodily state, plays a critical role in physical, cognitive, emotional and social well-being. Regarding physical well-being, contemporary models of exercise regulation incorporate interoceptive processes in the regulation of physical exertion. Top-down processes continuously monitor the physiological condition of the body to ensure allostasis is maintained, however, flagged perturbations also appear to influence these higher order processes in return. More specifically, enhancing one's physiological arousal by means of physical activity is a viable way of manipulating the afferent input entering the interoceptive system, appearing to optimise the integration of early sensory stimulation with later affective responses. Despite this, the relationship between physical activity and top-down regulation is underrepresented in interoceptive research. We here address this gap by integrating findings from different disciplines to support the overlapping mechanisms, with the hope of stimulating further research in this field. Developing our understanding of how interoceptive processes are shaped by physical activity could hold significant clinical implications considering the impact of interoceptive deficits to mental health and well-being.
Collapse
Affiliation(s)
| | - Pandelis Perakakis
- Department of Social, Work, and Differential Psychology, Complutense University of Madrid, Spain.
| | - Manos Tsakiris
- Department of Psychology, Royal Holloway, University of London, UK; Department of Behavioural and Cognitive Sciences, Faculty of Humanities, Education and Social Sciences, University of Luxembourg, Luxembourg
| | - Mirko Schmidt
- Institute of Sport Science, University of Bern, Switzerland
| |
Collapse
|
|
12
|
Chies AB, Spadella MA, de Oliveira PR, Domeniconi RF, de Mello Santos T, Moreira RP, Rosales CB, Casarini DE, Navar LG. Exercise-Induced Modulation of Angiotensin II Responses in Femoral Veins From 2-Kidney-1-Clip Hypertensive Rats. Front Physiol 2021; 12:620438. [PMID: 33897446 PMCID: PMC8058411 DOI: 10.3389/fphys.2021.620438] [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: 10/22/2020] [Accepted: 03/15/2021] [Indexed: 11/17/2022] Open
Abstract
The present study investigated the angiotensin II (Ang II) responses in rat femoral veins taken from 2-kidney-1clip (2K1C) hypertensive rats at 4 weeks after clipping, as well as the effects of exercise on these responses. In this manner, femoral veins taken from 2K1C rats kept at rest or exposed to acute exercise or to exercise training were challenged with Ang II or endothelin-1 (ET-1) in organ bath. Simultaneously, the presence of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were determined in these preparations by western blotting. In these experiments, femoral veins exhibited subdued Ang II responses. However, after nitric oxide (NO) synthesis blockade, the responses were higher in the femoral veins taken from animals kept at rest [0.137(0.049–0.245); n = 10] than those obtained in trained animals kept at rest [0.008(0.001–0.041); n = 10] or studied after a single bout of exercise [0.001(0.001–0.054); n = 11]. In preparations in which, in addition to NO synthesis, both the local production of prostanoids and the action of ET-1 on type A (ETA) or B (ETB) receptors were inhibited, the differences induced by exercise were no longer observed. In addition, neither ET-1 responses nor the presence of COX-1 and COX-2 in these preparations were modified by the employed exercise protocols. In conclusion, NO maintains Ang II responses reduced in femoral veins of 2K1C animals at rest. However, vasodilator prostanoids as well as other relaxing mechanisms, activated by ETB stimulation, are mobilized by exercise to cooperate with NO in order to maintain controlled Ang II responses in femoral veins.
Collapse
Affiliation(s)
| | | | | | | | | | - Roseli Peres Moreira
- Department of Medicine, Nephrology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Carla B Rosales
- Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, LA, United States
| | - Dulce Elena Casarini
- Department of Medicine, Nephrology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Luis Gabriel Navar
- Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, LA, United States
| |
Collapse
|
|
13
|
Rahimi S, Peeri M, Azarbayjani MA, Anoosheh L, Ghasemzadeh E, Khalifeh N, Noroozi-Mahyari S, Deravi S, Saffari-Anaraki S, Hemat Zangeneh F, Salari AA. Long-term exercise from adolescence to adulthood reduces anxiety- and depression-like behaviors following maternal immune activation in offspring. Physiol Behav 2020; 226:113130. [PMID: 32791182 DOI: 10.1016/j.physbeh.2020.113130] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 08/04/2020] [Accepted: 08/07/2020] [Indexed: 01/08/2023]
Abstract
Maternal immune activation is an environmental risk factor for the development of neuropsychiatric disorders such as anxiety and depression later in life. There is an urgent need to develop therapeutic strategies for treating or preventing psychiatric disorders with developmental origins. There is important information that physical exercise is a therapeutic strategy for treating anxiety and depression-related disorders. This study set out to determine the long-term effects of exercise on anxiety and depression-like behaviors following maternal immune activation in adult offspring. Pregnant mice were treated with lipopolysaccharides (LPS) or vehicle. Then offspring were subjected to a combination of different exercise protocols including voluntary running wheel, swimming, and treadmill exercises from adolescence to adulthood. Anxiety and depression-related symptoms in adult offspring were evaluated using open field, elevated plus maze, sucrose preference test, and forced swim test. The hypothalamic-pituitary-adrenal (HPA) axis reactivity was assessed by measuring corticosterone in serum. We also measured oxytocin, malondialdehyde, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 in the brain of adult offspring. Our findings indicated that long-term exercise significantly decreased anxiety- and depression-like behaviors in offspring prenatally exposed to maternal immune activation. The exercise also decreased corticosterone levels in the serum, and increased oxytocin and IL-10 levels in the brain of these offspring; whereas no significant alterations in TNF-α, IL-1β, IL-6 were found. Taken together, this study suggests that exercise might be a therapeutic strategy for the treatment of anxiety and depression-related behaviors following maternal immune activation in offspring.
Collapse
Affiliation(s)
- Samira Rahimi
- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Maghsoud Peeri
- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
| | | | - Leila Anoosheh
- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Elham Ghasemzadeh
- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Niloofar Khalifeh
- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Safoora Noroozi-Mahyari
- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Salome Deravi
- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Shadi Saffari-Anaraki
- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Fatemeh Hemat Zangeneh
- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Ali-Akbar Salari
- Salari Institute of Cognitive and Behavioral Disorders (SICBD), Alborz, Karaj, Iran
| |
Collapse
|
|
14
|
Rocha-Santos C, Braga DC, Ceroni A, Michelini LC. Activity-Dependent Neuroplastic Changes in Autonomic Circuitry Modulating Cardiovascular Control: The Essential Role of Baroreceptors and Chemoreceptors Signaling. Front Physiol 2020; 11:309. [PMID: 32328002 PMCID: PMC7160511 DOI: 10.3389/fphys.2020.00309] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 03/19/2020] [Indexed: 01/09/2023] Open
Abstract
Aerobic exercise training improves the autonomic control of the circulation. Emerging evidence has shown that exercise induces neuroplastic adaptive changes in preautonomic circuitry controlling sympathetic/parasympathetic outflow to heart and vessels. The mechanisms underlying neuronal plasticity are, however, incompletely understood. Knowing that sinoaortic denervation blocks training-induced cardiovascular benefits, we investigate whether baroreceptors’ and chemoreceptors’ signaling are able to drive neuronal plasticity within medullary and supramedullary pathways controlling autonomic outflow. Male Wistar rats submitted to sinoaortic denervation (SAD) or dopamine β-hydroxylase-saporin lesion (DBHx) and respective controls (SHAM) were allocated to training (T) or sedentary (S) protocols for 8 weeks. After hemodynamic measurements at rest, rats were deeply anesthetized for brain harvesting. The density of DBH and oxytocin (OT) cell bodies and terminals were analyzed in brainstem and hypothalamic brain areas (double immunofluorescence reactions, optic and confocal microscopy). In SHAM rats training augmented the density of DBH+ neurons in the nucleus of solitary tract, increased the density of ascending NORergic projections and the number of DBH+ boutons contacting preautonomic OT+ neurons into paraventricular hypothalamic preautonomic nuclei, augmented the density of local OTergic neurons and enhanced the density of OT+ terminals targeting brainstem autonomic areas. These plastic changes occurred simultaneously with reduced sympathetic/increased parasympathetic activity, augmented baroreflex sensitivity and reduced resting heart rate. SAD reduced the density of both DBH+ fibers ascending from brainstem to paraventricular nucleus of hypothalamus and preautonomic OT+ neurons projecting to the brainstem, abrogated training-induced plastic changes and autonomic adaptive responses without changing the treadmill performance. Minor neuroplastic changes with preserved baroreflex sensitivity were observed in trained rats after partial selective disruption of ascending NORergic projections. Our data indicated that afferent inputs conveyed by arterial baroreceptors and chemoreceptors are the main stimuli to drive both inactivity-induced and activity-dependent neuroplasticity within the autonomic circuitry.
Collapse
Affiliation(s)
- Carla Rocha-Santos
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Douglas Costa Braga
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Alexandre Ceroni
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Lisete C Michelini
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| |
Collapse
|
|
15
|
Qi J, Yu XJ, Fu LY, Liu KL, Gao TT, Tu JW, Kang KB, Shi XL, Li HB, Li Y, Kang YM. Exercise Training Attenuates Hypertension Through TLR4/MyD88/NF-κB Signaling in the Hypothalamic Paraventricular Nucleus. Front Neurosci 2019; 13:1138. [PMID: 31708733 PMCID: PMC6821652 DOI: 10.3389/fnins.2019.01138] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Accepted: 10/09/2019] [Indexed: 12/20/2022] Open
Abstract
Exercise training (ExT) is beneficial for cardiovascular health, yet the central mechanism by which aerobic ExT attenuates the hypertensive responses remains unclear. Activation of pro-inflammatory cytokines (PICs) in the hypothalamic paraventricular nucleus (PVN) is important for the sympathoexcitation and hypertensive response. We thus hypothesized that aerobic ExT can decrease the blood pressure of hypertensive rats by reducing the levels of PICs through TLR4/MyD88/NF-κB signaling within the PVN. To examine this hypothesis, two-kidney-one-clip (2K1C) renovascular hypertensive rats were assigned to two groups: sedentary or exercise training and examined for 8 weeks. At the same time, bilateral PVN infusion of vehicle or TAK242, a TLR4 inhibitor, was performed on both groups. As a result, the systolic blood pressure (SBP), renal sympathetic nerve activity (RSNA) and plasma levels of norepinephrine (NE), epinephrine (EPI) were found significantly increased in 2K1C hypertensive rats. These rats also had higher levels of Fra-like activity, NF-κB p65 activity, TLR4, MyD88, IL-1β and TNF-α in the PVN than SHAM rats. Eight weeks of ExT attenuated the RSNA and SBP, repressed the NF-κB p65 activity, and reduced the increase of plasma levels of NE, EPI, and the expression of Fra-like, TLR4, MyD88, IL-1β and TNF-α in the PVN of 2K1C rats. These findings are highly similar to the results in 2K1C rats with bilateral PVN infusions of TLR4 inhibitor (TAK242). This suggests that 8 weeks of aerobic ExT may decrease blood pressure in hypertensive rats by reducing the PICs activation through TLR4/MyD88/NF-κB signaling within the PVN, and thus delays the progression of 2K1C renovascular hypertension.
Collapse
Affiliation(s)
- Jie Qi
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.,Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an, China
| | - Xiao-Jing Yu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.,Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an, China
| | - Li-Yan Fu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.,Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an, China
| | - Kai-Li Liu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.,Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an, China
| | - Tian-Tian Gao
- School of Clinical Medicine, Xi'an Jiaotong University, Xi'an, China
| | - Jia-Wei Tu
- School of Clinical Medicine, Xi'an Jiaotong University, Xi'an, China
| | - Kai B Kang
- Department of Ophthalmology and Visual Sciences, The University of Illinois at Chicago, Chicago, IL, United States
| | - Xiao-Lian Shi
- Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Hong-Bao Li
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.,Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an, China
| | - Ying Li
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.,Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an, China
| | - Yu-Ming Kang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.,Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an, China
| |
Collapse
|
|
16
|
Resistance training improves cardiovascular autonomic control and biochemical profile of rats exposed to Western diet in the perinatal period. Rev Port Cardiol 2019; 38:337-345. [PMID: 31227291 DOI: 10.1016/j.repc.2018.08.009] [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] [Received: 02/14/2018] [Revised: 07/11/2018] [Accepted: 08/24/2018] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION AND OBJECTIVES Consumption of a Western diet during the perinatal period is associated with development of cardiovascular disease. Resistance training (RT) has been used to treat cardiovascular disorders. The aim of this work was to assess the effect of RT on cardiometabolic disorders in rats exposed to a Western diet in the perinatal period. METHODS Female Wistar rats were fed with control or Western diet during pregnancy and lactation. The pups were divided into three groups: Control (C), Western Diet Sedentary (WDS) and Western Diet + RT (WDRT). At 60 days of age, all animals started the RT protocol (five times a week for four weeks). At the end, blood pressure was recorded for analysis of heart rate variability and baroreflex sensitivity (BRS). Blood samples were collected for biochemical analysis. RESULTS RT reduced blood pressure and vascular sympathetic modulation and increased BRS. There were improvements in biochemical profile, with reductions in fasting blood glucose, total cholesterol and low-density lipoprotein, and an increase in high-density lipoprotein. CONCLUSION RT led to beneficial adaptations in the cardiovascular system, mediated by changes in the mechanisms of autonomic control and biochemical profile of animals exposed to a Western diet in the perinatal period.
Collapse
|
|
17
|
Yüksel O, Ateş M, Kızıldağ S, Yüce Z, Koç B, Kandiş S, Güvendi G, Karakılıç A, Gümüş H, Uysal N. Regular Aerobic Voluntary Exercise Increased Oxytocin in Female Mice: The Cause of Decreased Anxiety and Increased Empathy-Like Behaviors. Balkan Med J 2019; 36:257-262. [PMID: 31140236 PMCID: PMC6711252 DOI: 10.4274/balkanmedj.galenos.2019.2018.12.87] [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] [Indexed: 01/12/2023] Open
Abstract
Background: It is known that regular physical activity reduces anxiety. Low anxiety levels affect mood, emotions, and empathy. Oxytocin is a powerful hormone that regulates social interaction, sexual reproduction, maternal–infant bonding, milk release, empathy, and anxiety. Empathy is an important behavior in the living community; and also important for sportsmen during sportive competition and daily living life, because sportsmen are also role model of people. Aims: To investigate the effects of voluntary physical activity on oxytocin, anxiety, and empathy levels as well as the relationship between them. Study Design: Animal experiment. Methods: Male and female mice were made to exercise in running wheel cages for 6 weeks. Their empathy and anxiety levels were evaluated by using Helping Behavior test and elevated plus maze and open field test, respectively. And then the brain and blood oxytocin levels were measured. Results: Empathy-like behavior was improved in both genders of the exercise groups (door-opening time decreased in both genders of exercise groups, p for both=0.0001). As a response to exercise, both the brain and serum oxytocin levels increased in female mice (both of p=0.0001); however, in males, oxytocin levels increased in only the brain (p<0.05). Anxiety levels decreased in all the exercise groups (increased time spent in the middle area of open field test, both genders, p=0.002; increased time spent in the open arms of elevated plus maze test, females p=0.004, males p=0.0001). There was a strong negative correlation between serum oxytocin levels and door opening time of helping behavior equipment, and moderate negative correlation was found between the brain oxytocin levels and door-opening time of helping behavior equipment in females. However, there was no correlation between both the brain and serum oxytocin levels and empathy behavior in males. But there were very strong positive correlations between low anxiety indicators and both the brain and serum oxytocin levels in both the genders. Conclusion: Voluntary physical activity decreases anxiety and increases empathy-like behavior in mice; which is associated with increased oxytocin levels in female mice but not in male mice. Further research is required to investigate the mechanisms of exercise effect on anxiety and empathic brain pathways in males.
Collapse
Affiliation(s)
- Oğuz Yüksel
- Department of Sports Medicine, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Mehmet Ateş
- College of Vocational School of Health Services, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Servet Kızıldağ
- College of Vocational School of Health Services, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Zeynep Yüce
- Department of Medical Biology and Genetics, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Başar Koç
- Department of Physiology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Sevim Kandiş
- Department of Physiology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Güven Güvendi
- Department of Physiology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Aslı Karakılıç
- Department of Physiology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Hikmet Gümüş
- Department of Physiology, Dokuz Eylül University School of Medicine, İzmir, Turkey,Dokuz Eylül University School of Sport Sciences and Technology, İzmir, Turkey
| | - Nazan Uysal
- Department of Physiology, Dokuz Eylül University School of Medicine, İzmir, Turkey
| |
Collapse
|
|
18
|
Farley D, Piszczek Ł, Bąbel P. Why is running a marathon like giving birth? The possible role of oxytocin in the underestimation of the memory of pain induced by labor and intense exercise. Med Hypotheses 2019; 128:86-90. [PMID: 31203917 DOI: 10.1016/j.mehy.2019.05.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Revised: 04/14/2019] [Accepted: 05/10/2019] [Indexed: 01/09/2023]
Abstract
Pain can be overestimated, underestimated or reported accurately at recall. The way pain is remembered seems to depend on certain factors, including the type of pain or, in other words, its cause, the context, and the meaning it has for the person suffering from it. For instance, episodes of chronic pain, as well as pain related to surgery, are often overestimated at recall. Interestingly, research shows that pain induced by parturition or marathon running is often underestimated at recall despite the fact that both are not only physically grueling but also emotionally intense experiences. However, both processes can likewise be considered positive events, as opposed to most that involve pain. On the neurophysiological level, one of the similarities between giving birth and running a marathon is the particular involvement of the oxytocin system. Oxytocin is involved both in parturition and intense exercise, for various reasons. During labor, oxytocin mediates uterine contractions, while in the case of extensive running it might be involved in the maintenance of fluid balance. It also has well-documented analgesic properties and plays an important role in memory formation and recall. It has been suggested that oxytocin modulates the output of the central nucleus of the amygdala (CeA) during the fear recall. Moreover, it has been demonstrated that oxytocin can impair fear learning and influence the memory of both positive and negative emotionally salient stimuli. We propose that the reason for pain to be remembered in a more favorable light is the central action of oxytocin in the central nucleus of the amygdala, first and foremost during the encoding phase.
Collapse
Affiliation(s)
- Dominika Farley
- Jagiellonian University, Institute of Psychology, Pain Research Group, Poland.
| | | | - Przemysław Bąbel
- Jagiellonian University, Institute of Psychology, Pain Research Group, Poland
| |
Collapse
|
|
19
|
Santana MNS, De Melo VU, Macedo FN, Barreto AS, Vidal-Santos R, Neto M, dos Santos MRV, Santana-Filho VJ. Resistance training improves cardiovascular autonomic control and biochemical profile of rats exposed to a Western diet in the perinatal period. REVISTA PORTUGUESA DE CARDIOLOGIA (ENGLISH EDITION) 2019. [DOI: 10.1016/j.repce.2018.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
|
|
20
|
Adamo S, Pigna E, Lugarà R, Moresi V, Coletti D, Bouché M. Skeletal Muscle: A Significant Novel Neurohypophyseal Hormone-Secreting Organ. Front Physiol 2019; 9:1885. [PMID: 30670984 PMCID: PMC6331439 DOI: 10.3389/fphys.2018.01885] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2018] [Accepted: 12/12/2018] [Indexed: 01/08/2023] Open
Affiliation(s)
- Sergio Adamo
- Section of Histology & Medical Embryology, Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Interuniversity Institute of Myology, Sapienza University of Rome, Rome, Italy
| | - Eva Pigna
- Section of Histology & Medical Embryology, Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Interuniversity Institute of Myology, Sapienza University of Rome, Rome, Italy
| | - Rosamaria Lugarà
- Section of Histology & Medical Embryology, Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Interuniversity Institute of Myology, Sapienza University of Rome, Rome, Italy
| | - Viviana Moresi
- Section of Histology & Medical Embryology, Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Interuniversity Institute of Myology, Sapienza University of Rome, Rome, Italy
| | - Dario Coletti
- Section of Histology & Medical Embryology, Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Interuniversity Institute of Myology, Sapienza University of Rome, Rome, Italy.,Sorbonne Université, CNRS UMR 8256-INSERM ERL U1164, Biological Adaptation and Aging B2A, Paris, France
| | - Marina Bouché
- Section of Histology & Medical Embryology, Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Interuniversity Institute of Myology, Sapienza University of Rome, Rome, Italy
| |
Collapse
|
|
21
|
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.
Collapse
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
| |
Collapse
|
|
22
|
Lerman B, Harricharran T, Ogunwobi OO. Oxytocin and cancer: An emerging link. World J Clin Oncol 2018; 9:74-82. [PMID: 30254962 PMCID: PMC6153127 DOI: 10.5306/wjco.v9.i5.74] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 07/11/2018] [Accepted: 08/06/2018] [Indexed: 02/06/2023] Open
Abstract
The neuropeptide hormone oxytocin, which is released from the posterior pituitary gland, is involved in a number of physiological processes. Understanding of its effects is gradually increasing due to new research in this area. While mostly recognized as a reproductive system hormone, oxytocin also regulates other organ systems such as the brain and cardiovascular system. Recently, research has focused on unraveling its involvement in cancer, and emerging evidence suggests a potential role for oxytocin as a cancer biomarker. This review summarizes observations linking oxytocin and cancer, with a special emphasis on prostate cancer, where it may promote cell proliferation. Research suggests that oxytocin effects may depend on cell type, concentration of the hormone, its interactions with other hormones in the microenvironment, and the precise localization of its receptor on the cell membrane. Future research is needed to further elucidate the involvement of oxytocin in cancer, and whether it could be a clinical cancer biomarker or therapeutic target.
Collapse
Affiliation(s)
- Ben Lerman
- Department of Biological Sciences, Hunter College of the City University of New York, New York, NY 10065, United States
| | - Trisheena Harricharran
- Department of Biological Sciences, Hunter College of the City University of New York, New York, NY 10065, United States
- the Graduate Center Departments of Biology and Biochemistry, the City University of New York, New York, NY 10016, United States
| | - Olorunseun O Ogunwobi
- Department of Biological Sciences, Hunter College of the City University of New York, New York, NY 10065, United States
- the Graduate Center Departments of Biology and Biochemistry, the City University of New York, New York, NY 10016, United States
- Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10065, United States
| |
Collapse
|
|
23
|
Raquel HDA, Ferreira NZ, Lucchetti BFC, Falquetto B, Pinge-Filho P, Michelini LC, Martins-Pinge MC. The essential role of hypothalamic paraventricular nucleus nNOS in the modulation of autonomic control in exercised rats. Nitric Oxide 2018; 79:14-24. [DOI: 10.1016/j.niox.2018.07.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Revised: 05/24/2018] [Accepted: 07/02/2018] [Indexed: 12/31/2022]
|
|
24
|
Santos CR, Ruggeri A, Ceroni A, Michelini LC. Exercise training abrogates age-dependent loss of hypothalamic oxytocinergic circuitry and maintains high parasympathetic activity. J Neuroendocrinol 2018; 30:e12601. [PMID: 29656427 DOI: 10.1111/jne.12601] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Accepted: 04/05/2018] [Indexed: 11/27/2022]
Abstract
Neuroanatomical studies associating neuronal tract tracing and immunohistochemistry identified reciprocal (ascending noradrenergic/descending oxytocinergic, OTergic) connections between brainstem cardiovascular nuclei and the paraventricular hypothalamic nucleus (PVN). Previous functional studies indicated that exercise training (T) augmented the expression/activity of OTergic pathway and improve the autonomic control of the heart. Knowing that ageing is associated with autonomic dysfunction and sinoaortic denervation blocked T-induced beneficial effects, we hypothesized that T was able to reduce age-dependent impairment by improving the afferent signaling to PVN and augmenting OTergic modulation of cardiovascular control. We evaluated the combined effects of T and age on plastic remodeling of ascending dopamine β-hydroxylase (DBH+) and descending OT+ pathways and correlated them with cardiovascular parameters. Male Wistar rats were submitted to T or kept sedentary for 8 weeks. After evaluating arterial pressure, heart rate (HR), their variabilities and spectral components in conscious rats at rest, brains were harvested to analyze the plastic remodeling of brain autonomic nuclei (immunofluorescence + confocal microscopy). The density of DBH+ neurons within the nucleus of solitary tract (NTS) and caudal ventrolateral medulla, the number of DBH+ terminals overlapping OT+ neurons in PVN preautonomic nuclei, as well as the density of OT+ neurons and their projections to NTS and dorsal motor nucleus of the vagus were markedly reduced in S rats during 8-weeks of inactivity In contrast, these effects were completely blocked by T and reversed to a large augmentation of DBH+ and OT+ densities in both cell bodies and terminals within autonomic nuclei and target areas. All plastic changes observed correlated positively with parasympathetic activity to the heart (HF-PI, but not with LF-PI) and negatively with resting HR. Data indicate that T, by increasing beneficial neuroplastic adaptive changes within brainstem-PVN reciprocal network, abrogates age-dependent deleterious remodeling and augments parasympathetic modulation of the heart, therefore improving autonomic function. This article is protected by copyright. All rights reserved.
Collapse
Affiliation(s)
- Carla R Santos
- Department of Physiology, Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo/SP, Brazil
| | - Adriana Ruggeri
- Department of Physiology, Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo/SP, Brazil
| | - Alexandre Ceroni
- Department of Physiology, Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo/SP, Brazil
| | - Lisete C Michelini
- Department of Physiology, Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo/SP, Brazil
| |
Collapse
|
|
25
|
Gartner SN, Aidney F, Klockars A, Prosser C, Carpenter EA, Isgrove K, Levine AS, Olszewski PK. Intragastric preloads of l-tryptophan reduce ingestive behavior via oxytocinergic neural mechanisms in male mice. Appetite 2018; 125:278-286. [PMID: 29471071 DOI: 10.1016/j.appet.2018.02.015] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 02/09/2018] [Accepted: 02/15/2018] [Indexed: 11/29/2022]
Abstract
Human and laboratory animal studies suggest that dietary supplementation of a free essential amino acid, l-tryptophan (TRP), reduces food intake. It is unclear whether an acute gastric preload of TRP decreases consumption and whether central mechanisms underlie TRP-driven hypophagia. We examined the effect of TRP administered via intragastric gavage on energy- and palatability-induced feeding in mice. We sought to identify central mechanisms through which TRP suppresses appetite. Effects of TRP on consumption of energy-dense and energy-dilute tastants were established in mice stimulated to eat by energy deprivation or palatability. A conditioned taste aversion (CTA) paradigm was used to assess whether hypophagia is unrelated to sickness. c-Fos immunohistochemistry was employed to detect TRP-induced activation of feeding-related brain sites and of oxytocin (OT) neurons, a crucial component of satiety circuits. Also, expression of OT mRNA was assessed with real-time PCR. The functional importance of OT in mediating TRP-driven hypophagia was substantiated by showing the ability of OT receptor blockade to abolish TRP-induced decrease in feeding. TRP reduced intake of energy-dense standard chow in deprived animals and energy-dense palatable chow in sated mice. Anorexigenic doses of TRP did not cause a CTA. TRP failed to affect intake of palatable yet calorie-dilute or noncaloric solutions (10% sucrose, 4.1% Intralipid or 0.1% saccharin) even for TRP doses that decreased water intake in thirsty mice. Fos analysis revealed that TRP increases activation of several key feeding-related brain areas, especially in the brain stem and hypothalamus. TRP activated hypothalamic OT neurons and increased OT mRNA levels, whereas pretreatment with an OT antagonist abolished TRP-driven hypophagia. We conclude that intragastric TRP decreases food and water intake, and TRP-induced hypophagia is partially mediated via central circuits that encompass OT.
Collapse
Affiliation(s)
| | | | | | - Colin Prosser
- Dairy Goat Co-operative (NZ) Ltd, Hamilton, New Zealand
| | | | | | - Allen S Levine
- Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN, USA
| | - Pawel K Olszewski
- University of Waikato, Hamilton, New Zealand; Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN, USA.
| |
Collapse
|
|
26
|
Bulut EC, Abueid L, Ercan F, Süleymanoğlu S, Ağırbaşlı M, Yeğen BÇ. Treatment with oestrogen-receptor agonists or oxytocin in conjunction with exercise protects against myocardial infarction in ovariectomized rats. Exp Physiol 2018; 101:612-27. [PMID: 26958805 DOI: 10.1113/ep085708] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Accepted: 03/04/2016] [Indexed: 01/23/2023]
Abstract
NEW FINDINGS What is the central question of this study? Could the activation of oxytocin or oestrogen receptors be protective against myocardial injury after ovariectomy? If so, would exercising have an additional ameliorating effect? What is the main finding and its importance? The results revealed that when accompanied by exercise, both oestrogen receptor agonists and oxytocin improved cardiac dysfunction, inhibited the generation of pro-inflammatory cytokines and reduced myocardial injury in ovariectomized female rats, suggesting a new approach for protecting postmenopausal women against ischaemia-induced myocardial injury. To investigate the putative protective effects of oxytocin or oestrogen receptor agonists against myocardial injury of ovariectomized sedentary or exercised rats, female Sprague-Dawley rats assigned to sham-operated control and ovariectomized (OVX) groups were kept sedentary or undertook swimming exercise for 4 weeks and were treated with saline, an oestrogen receptor (ER) β (DPN) or ERα agonist (PPT) or oxytocin. Ovariectomy increased weight gain and anxiety in sedentary rats, whereas exercise prevented weight gain. When accompanied by exercise, both ER agonists and oxytocin inhibited weight gain and anxiety; oxytocin, in the absence or presence of exercise, increased the left ventricular diastolic dimensions and ejection fraction, whereas ER agonists also increased left ventricular diameter when given to exercised rats. Upon the induction of myocardial ischaemia-reperfusion in the OVX rats, plasma creatine kinase-(muscle-brain) was depressed by PPT and oxytocin, whereas DPN, PPT and OT reduced plasminogen activator inhibitor-1 concentrations. The increased tumour necrosis factor-α concentration in OVX rats was also suppressed by exercise or DPN, PPT or oxytocin treatments, whereas the interleukin-6 concentration was diminished by all the treatments when given in conjunction with exercise. Disorganization of cardiac muscle fibres was reduced in all exercised rats. Oestrogen receptor agonists, as well as oxytocin, in conjunction with exercise may be effective new therapeutics to protect against myocardial ischaemia in postmenopausal women.
Collapse
Affiliation(s)
- Erman Caner Bulut
- Department of Physiology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Leyla Abueid
- Department of Physiology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Feriha Ercan
- Department of Histology & Embryology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Selami Süleymanoğlu
- Department of Pediatric Cardiology, Gulhane Military Medical Academy, Istanbul, Turkey
| | - Mehmet Ağırbaşlı
- Department of Cardiology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Berrak Ç Yeğen
- Department of Physiology, School of Medicine, Marmara University, Istanbul, Turkey
| |
Collapse
|
|
27
|
Alizadeh AM, Heydari Z, Rahimi M, Bazgir B, Shirvani H, Alipour S, Heidarian Y, Khalighfard S, Isanejad A. Oxytocin mediates the beneficial effects of the exercise training on breast cancer. Exp Physiol 2017; 103:222-235. [PMID: 29143998 DOI: 10.1113/ep086463] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2017] [Accepted: 11/13/2017] [Indexed: 12/13/2022]
Abstract
NEW FINDINGS What is the central question of this study? We hypothesized that potential anti-tumour effects of exercise training might be mediated by oxytocin and explored the underlying mechanisms in a mouse model of breast cancer. What is the main finding and its importance? Interval exercise training, by inducing oxytocin secretion, may reduce the activity of the PI3K/Akt and ERK pathways, and consequently, results in a smaller tumour volume in a mouse model of breast cancer. Exercise training can affect the growth of breast tumours. We hypothesized that exercise training might reduce breast tumour growth by inducing oxytocin (OT) secretion and its related signalling pathways, such as PI3K/Akt and ERK. Therefore, 56 BALB/c mice were equally divided into seven groups to study the effects of OT and atosiban (an oxytocin receptor antagonist) together with interval exercise training on mammary tumour growth, as well as tumour-related signalling pathways, including PI3K/Akt and ERK. Animal weight, OT plasma concentration, tumour weight and volume were measured at the end of the study. PI3K/Akt and ERK were evaluated by Western blot and qPCR assays. The results showed that OT plasma concentration was significantly increased in trained animals. The volume and weight of tumours were decreased significantly after both exercise training and OT administration. The expression of genes involved in tumour cell proliferation, such as PI3KR2, Akt and mTOR, was notably lower in the exercise-trained and OT-treated groups. Furthermore, the expression of genes involved in cell apoptosis, such as caspase-3 and Bax, was significantly increased in the tumour tissues. In addition, Western blot results showed that phosphorylated Akt and ERK were significantly decreased in the exercise training and OT groups compared with the tumour group. Interestingly, atosiban reversed these effects. These results indicated that interval exercise training, acting via OT secretion, may reduce PI3K/Akt and ERK axis activities, and consequently, decrease tumour volume and weight in a mouse model of breast cancer.
Collapse
Affiliation(s)
- Ali Mohammad Alizadeh
- Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Breast Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Heydari
- Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mostafa Rahimi
- Department of Physical Education and Sport Sciences, University of Shahrekord, Shahrekord, Iran
| | - Behzad Bazgir
- Exercise Physiology Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Hossein Shirvani
- Exercise Physiology Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Sadaf Alipour
- Breast Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Yassaman Heidarian
- Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Solmaz Khalighfard
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Amin Isanejad
- Immunoregulation Research Center, Shahed University, Tehran, Iran.,Department of Physical Education and Sport Sciences, Shahed University, Tehran, Iran
| |
Collapse
|
|
28
|
Exercise training reverses the negative effects of chronic L-arginine supplementation on insulin sensitivity. Life Sci 2017; 191:17-23. [DOI: 10.1016/j.lfs.2017.10.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Revised: 09/24/2017] [Accepted: 10/01/2017] [Indexed: 12/14/2022]
|
|
29
|
Chies AB, de Oliveira PB, Rossignoli PDS, Baptista RDFF, de Lábio RW, Payão SLM. Prostanoids counterbalance the synergism between endothelin-1 and angiotensin II in mesenteric veins of trained rats. Peptides 2017; 88:67-73. [PMID: 28012855 DOI: 10.1016/j.peptides.2016.12.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Revised: 12/15/2016] [Accepted: 12/20/2016] [Indexed: 11/30/2022]
Abstract
Exercise-induced adaptations of the modulating mechanisms that influence the angiotensin (Ang II) responses assume different features depending on the venous bed. In femoral veins, exercise mobilizes vasodilator prostanoids to cooperate with NO in order to maintain reduced Ang II responses. On the other hand, exercise's influence on the Ang II responses in veins that drain blood from the mesenteric region has been poorly described. Therefore, the present study aimed to identify the effects of a single bout of exercise, as well as exercise training, on the Ang II responses in mesenteric veins. The present study also aimed to investigate the involvement of prostanoids, NO and ET-1 in eventual exercise-induced modifications in these veins. To this end, mesenteric veins taken from resting-sedentary, exercised-sedentary, resting-trained and exercised-trained animals were studied in organ baths. In addition, the mRNA expression of prepro-endothelin-1 (ppET-1), as well as that of the ETA and ETB receptors, were quantified by real-time PCR in these veins. The results show that, either in absence or in presence of L-NAME, the Ang II responses were not different between groups. In the presence of indomethacin, higher Ang II responses were observed in the resting-trained animals than in the resting-sedentary animals. This difference, however, disappeared when L-NAME, BQ-123 or BQ-788 were added during incubation. In addition, no differences in ppET-1, ETA or ETB mRNA expression were observed between groups. Furthermore, in the presence of PD123,319, the Ang II responses in the exercised-sedentary animals were higher than those in the resting-sedentary animals. In conclusion, exercise training mobilizes endothelin-1 (ET-1) to reinforce the Ang II-induced responses mainly through ETA activation. On the other hand, vasodilator prostanoids are mobilized to act in parallel with NO in order to counterbalance the Ang II responses that have been potentiated by ET-1 in these trained animals.
Collapse
|
|
30
|
Experimental Evidences Supporting Training-Induced Benefits in Spontaneously Hypertensive Rats. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 999:287-306. [DOI: 10.1007/978-981-10-4307-9_16] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
|
|
31
|
Clark A, Mach N. Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes. J Int Soc Sports Nutr 2016; 13:43. [PMID: 27924137 PMCID: PMC5121944 DOI: 10.1186/s12970-016-0155-6] [Citation(s) in RCA: 324] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Accepted: 11/19/2016] [Indexed: 12/14/2022] Open
Abstract
Fatigue, mood disturbances, under performance and gastrointestinal distress are common among athletes during training and competition. The psychosocial and physical demands during intense exercise can initiate a stress response activating the sympathetic-adrenomedullary and hypothalamus-pituitary-adrenal (HPA) axes, resulting in the release of stress and catabolic hormones, inflammatory cytokines and microbial molecules. The gut is home to trillions of microorganisms that have fundamental roles in many aspects of human biology, including metabolism, endocrine, neuronal and immune function. The gut microbiome and its influence on host behavior, intestinal barrier and immune function are believed to be a critical aspect of the brain-gut axis. Recent evidence in murine models shows that there is a high correlation between physical and emotional stress during exercise and changes in gastrointestinal microbiota composition. For instance, induced exercise-stress decreased cecal levels of Turicibacter spp and increased Ruminococcus gnavus, which have well defined roles in intestinal mucus degradation and immune function. Diet is known to dramatically modulate the composition of the gut microbiota. Due to the considerable complexity of stress responses in elite athletes (from leaky gut to increased catabolism and depression), defining standard diet regimes is difficult. However, some preliminary experimental data obtained from studies using probiotics and prebiotics studies show some interesting results, indicating that the microbiota acts like an endocrine organ (e.g. secreting serotonin, dopamine or other neurotransmitters) and may control the HPA axis in athletes. What is troubling is that dietary recommendations for elite athletes are primarily based on a low consumption of plant polysaccharides, which is associated with reduced microbiota diversity and functionality (e.g. less synthesis of byproducts such as short chain fatty acids and neurotransmitters). As more elite athletes suffer from psychological and gastrointestinal conditions that can be linked to the gut, targeting the microbiota therapeutically may need to be incorporated in athletes’ diets that take into consideration dietary fiber as well as microbial taxa not currently present in athlete’s gut.
Collapse
Affiliation(s)
- Allison Clark
- Health Science Department, Open University of Catalonia (UOC), 08035 Barcelona, Spain
| | - Núria Mach
- Health Science Department, Open University of Catalonia (UOC), 08035 Barcelona, Spain ; Animal Genetics and Integrative Biology unit (GABI), INRA, AgroParis Tech, Université Paris-Saclay, 78352, Jouy-en-Josas, France
| |
Collapse
|
|
32
|
Oxytocin, a main breastfeeding hormone, prevents hypertension acquired in utero: A therapeutics preview. Biochim Biophys Acta Gen Subj 2016; 1861:3071-3084. [PMID: 27658996 DOI: 10.1016/j.bbagen.2016.09.020] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Revised: 08/29/2016] [Accepted: 09/16/2016] [Indexed: 02/07/2023]
Abstract
Hypertension is a major risk factor for ischemic heart disease and stroke, leading causes of morbidity and death worldwide. Intrauterine growth restriction (IUGR), caused by an excess of glucocorticoid exposure to the fetus, produces an imbalance in oxidative stress altering many biochemical and epigenetic gene transcription processes exposing the fetus and neonate to the 'thrifty' phenotype and pervasive polymorphisms appearance damaging health, cognitive, and behavioral processes in later life. OT is a major regulator of oxidative stress radicals that plays a major role in neonatal maturation of the central nervous system and many peripheral tissues expressing oxytocin/oxytocin-receptor (OT/OTR) system in the early postnatal period. OT and OTR are damaged by IUGR and early stress. This review highlights the fact that hypertension is likely to be a legacy of preterm birth due to IUGR and failure to meet nutritional needs in early infancy when fed formula instead of breastfeeding or human milk.
Collapse
|
|
33
|
Kenkel WM, Carter CS. Voluntary exercise facilitates pair-bonding in male prairie voles. Behav Brain Res 2015; 296:326-330. [PMID: 26409174 DOI: 10.1016/j.bbr.2015.09.028] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Revised: 09/16/2015] [Accepted: 09/21/2015] [Indexed: 10/23/2022]
Abstract
The neuropeptides oxytocin and vasopressin have been implicated in exercise, as well as monogamy and parental behavior. In this study, we compared behavioral and neuroendocrine effects of access to an exercise wheel vs. the sedentary state typical in lab animal housing. Male prairie voles (Microtus ochrogaster) were studied because of their extensive repertoire of social behaviors including pair bond formation and biparental care, which are influenced by oxytocin and vasopressin. Subjects in one group had access to a running wheel in their cage (wheel), and voluntarily ran approximately 1.5 km/day for six weeks; these animals were compared to males in standard housing conditions (n=10/group). Males allowed to exercise formed partner preferences significantly faster than controls and exhibited fewer oxytocin neurons, as measured by immunohistochemistry in the bed nucleus of the stria terminalis. We observed no differences in terms of anxiety-related behavior, or alloparental responsiveness. Males with a running wheel equipped cage gained more total body weight, and by the end of the six weeks were found to have less subcutaneous fat and larger testes as a percentage of bodyweight. The changes to gonadal regulation and pair-bonding behavior associated with voluntary exercise are discussed in terms of their possible relevance to the natural history of this species.
Collapse
Affiliation(s)
- William M Kenkel
- Department of Psychology, Northeastern University, Boston, MA 02115, United States; The Kinsey Institute, and Department of Biology, Indiana University, Bloomington, IN 47405, United States.
| | - C Sue Carter
- Department of Psychology, Northeastern University, Boston, MA 02115, United States; The Kinsey Institute, and Department of Biology, Indiana University, Bloomington, IN 47405, United States
| |
Collapse
|
|
34
|
Sladek CD, Michelini LC, Stachenfeld NS, Stern JE, Urban JH. Endocrine‐Autonomic Linkages. Compr Physiol 2015; 5:1281-323. [DOI: 10.1002/cphy.c140028] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
|
|
35
|
de Souza Mecawi A, Ruginsk SG, Elias LLK, Varanda WA, Antunes‐Rodrigues J. Neuroendocrine Regulation of Hydromineral Homeostasis. Compr Physiol 2015; 5:1465-516. [DOI: 10.1002/cphy.c140031] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
|
|
36
|
Abstract
Oxytocin is a neurohypophyseal hormone that is produced centrally by neurons in the paraventricular nucleus and supraoptic nucleus of the hypothalamus. It is released directly into higher brain centres and into the peripheral circulation where it produces a multitude of effects. Classically, oxytocin is known for inducing uterine contractions at parturition and milk ejection during suckling. Oxytocin also acts in a species and gender specific manner as an important neuromodulator. It can affect behaviours associated with stress and anxiety, as well social behaviours including sexual and relationship behaviours, and maternal care. Additionally, oxytocin has been shown to have a variety of physiological roles in peripheral tissues, many of which appear to be modulated largely by locally produced oxytocin, dispelling the notion that oxytocin is a purely neurohypophyseal hormone. Oxytocin levels are altered in several diseases and the use of oxytocin or its antagonists have been identified as a possible clinical intervention in the treatment of mood disorders and pain conditions, some cancers, benign prostatic disease and osteoporosis. Indeed, oxytocin has already been successful in clinical trials to treat autism and schizophrenia. This review will report briefly on the known functions of oxytocin, it will discuss in depth the data from recent clinical trials and highlight future targets for oxytocinergic modulation.
Collapse
|
|
37
|
Morgan JA, Corrigan F, Baune BT. Effects of physical exercise on central nervous system functions: a review of brain region specific adaptations. J Mol Psychiatry 2015; 3:3. [PMID: 26064521 PMCID: PMC4461979 DOI: 10.1186/s40303-015-0010-8] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Accepted: 04/08/2015] [Indexed: 12/15/2022] Open
Abstract
Pathologies of central nervous system (CNS) functions are involved in prevalent conditions such as Alzheimer's disease, depression, and Parkinson's disease. Notable pathologies include dysfunctions of circadian rhythm, central metabolism, cardiovascular function, central stress responses, and movement mediated by the basal ganglia. Although evidence suggests exercise may benefit these conditions, the neurobiological mechanisms of exercise in specific brain regions involved in these important CNS functions have yet to be clarified. Here we review murine evidence about the effects of exercise on discrete brain regions involved in important CNS functions. Exercise effects on circadian rhythm, central metabolism, cardiovascular function, stress responses in the brain stem and hypothalamic pituitary axis, and movement are examined. The databases Pubmed, Web of Science, and Embase were searched for articles investigating regional brain adaptations to exercise. Brain regions examined included the brain stem, hypothalamus, and basal ganglia. We found evidence of multiple regional adaptations to both forced and voluntary exercise. Exercise can induce molecular adaptations in neuronal function in many instances. Taken together, these findings suggest that the regional physiological adaptations that occur with exercise could constitute a promising field for elucidating molecular and cellular mechanisms of recovery in psychiatric and neurological health conditions.
Collapse
Affiliation(s)
- Julie A Morgan
- />University of Adelaide, School of Medicine, Discipline of Psychiatry, Psychiatric Neuroscience Laboratory, Adelaide, South Australia Australia
| | - Frances Corrigan
- />University of Adelaide, Discipline of Anatomy and Pathology, School of Medical Sciences, Adelaide, South Australia Australia
| | - Bernhard T Baune
- />University of Adelaide, School of Medicine, Discipline of Psychiatry, Psychiatric Neuroscience Laboratory, Adelaide, South Australia Australia
| |
Collapse
|
|
38
|
Vargas-Martínez F, Uvnäs-Moberg K, Petersson M, Olausson HA, Jiménez-Estrada I. Neuropeptides as neuroprotective agents: Oxytocin a forefront developmental player in the mammalian brain. Prog Neurobiol 2014; 123:37-78. [DOI: 10.1016/j.pneurobio.2014.10.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Accepted: 10/06/2014] [Indexed: 02/07/2023]
|
|
39
|
Lozić M, Greenwood M, Šarenac O, Martin A, Hindmarch C, Tasić T, Paton J, Murphy D, Japundžić-Žigon N. Overexpression of oxytocin receptors in the hypothalamic PVN increases baroreceptor reflex sensitivity and buffers BP variability in conscious rats. Br J Pharmacol 2014; 171:4385-98. [PMID: 24834854 DOI: 10.1111/bph.12776] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Revised: 04/24/2014] [Accepted: 05/08/2014] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND AND PURPOSE The paraventricular nucleus (PVN) of the hypothalamus is an important integrative site for neuroendocrine control of the circulation. We investigated the role of oxytocin receptors (OT receptors) in PVN in cardiovascular homeostasis. EXPERIMENTAL APPROACH Experiments were performed in conscious male Wistar rats equipped with a radiotelemetric device. The PVN was unilaterally co-transfected with an adenoviral vector (Ad), engineered to overexpress OT receptors, and an enhanced green fluorescent protein (eGFP) tag. Control groups: PVN was transfected with an Ad expressing eGFP alone or untransfected, sham rats (Wt). Recordings were obtained without and with selective blockade of OT receptors (OTX), during both baseline and stressful conditions. Baroreceptor reflex sensitivity (BRS) and cardiovascular short-term variability were evaluated using the sequence method and spectral methodology respectively. KEY RESULTS Under baseline conditions, rats overexpressing OT receptors (OTR) exhibited enhanced BRS and reduced BP variability compared to control groups. Exposure to stress increased BP, BP variability and HR in all rats. In control groups, but not in OTR rats, BRS decreased during stress. Pretreatment of OTR rats with OTX reduced BRS and enhanced BP and HR variability under baseline and stressful conditions. Pretreatment of Wt rats with OTX, reduced BRS and increased BP variability under baseline and stressful conditions, but only increased HR variability during stress. CONCLUSIONS AND IMPLICATIONS OT receptors in PVN are involved in tonic neural control of BRS and cardiovascular short-term variability. The failure of this mechanism could critically contribute to the loss of autonomic control in cardiovascular disease.
Collapse
Affiliation(s)
- Maja Lozić
- Institute of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia
| | | | | | | | | | | | | | | | | |
Collapse
|
|
40
|
Imanieh MH, Bagheri F, Alizadeh AM, Ashkani-Esfahani S. Oxytocin has therapeutic effects on cancer, a hypothesis. Eur J Pharmacol 2014; 741:112-23. [PMID: 25094035 DOI: 10.1016/j.ejphar.2014.07.053] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2014] [Revised: 07/20/2014] [Accepted: 07/22/2014] [Indexed: 01/25/2023]
Abstract
Oxytocin (OT) is the first peptide hormone structurally assessed and chemically synthesized in biologically active form. This hormone acts as an important factor in a human reproductive system particularly during pregnancy and lactation in women. So far, different therapeutic roles for OT have been identified as a spectrum from central and peripheral actions on male and female reproductive systems, circulatory system, musculoskeletal system, etc. Some in vitro and in vivo studies also revealed that OT is responsible for bivariate biological functions involved in cancer as following. By activating OT receptor in tumoral cells, OT enacts as a growth regulator, whether activator or inhibitor. Regarding the increase of OT in some conditions such as breastfeeding, exercise, and multiparity, we can relate the effect of these conditions on cancer with OT effects. Based on this hypothesis, we present a review on the effects of this neuropeptide on various types of cancer and also the influence of these conditions on the same cancer.
Collapse
Affiliation(s)
| | - Fereshte Bagheri
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Mohammad Alizadeh
- Cancer Research Center, Tehran University of Medical Sciences, PO Box 1419733141, Tehran, Iran.
| | | |
Collapse
|
|
41
|
Time-dependent effects of training on cardiovascular control in spontaneously hypertensive rats: role for brain oxidative stress and inflammation and baroreflex sensitivity. PLoS One 2014; 9:e94927. [PMID: 24788542 PMCID: PMC4006803 DOI: 10.1371/journal.pone.0094927] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Accepted: 03/20/2014] [Indexed: 12/26/2022] Open
Abstract
Baroreflex dysfunction, oxidative stress and inflammation, important hallmarks of hypertension, are attenuated by exercise training. In this study, we investigated the relationships and time-course changes of cardiovascular parameters, pro-inflammatory cytokines and pro-oxidant profiles within the hypothalamic paraventricular nucleus of the spontaneously hypertensive rats (SHR). Basal values and variability of arterial pressure and heart rate and baroreflex sensitivity were measured in trained (T, low-intensity treadmill training) and sedentary (S) SHR at weeks 0, 1, 2, 4 and 8. Paraventricular nucleus was used to determine reactive oxygen species (dihydroethidium oxidation products, HPLC), NADPH oxidase subunits and pro-inflammatory cytokines expression (Real time PCR), p38 MAPK and ERK1/2 expression (Western blotting), NF-κB content (electrophoretic mobility shift assay) and cytokines immunofluorescence. SHR-S vs. WKY-S (Wistar Kyoto rats as time control) showed increased mean arterial pressure (172±3 mmHg), pressure variability and heart rate (358±7 b/min), decreased baroreflex sensitivity and heart rate variability, increased p47phox and reactive oxygen species production, elevated NF-κB activity and increased TNF-α and IL-6 expression within the paraventricular nucleus of hypothalamus. Two weeks of training reversed all hypothalamic changes, reduced ERK1/2 phosphorylation and normalized baroreflex sensitivity (4.04±0.31 vs. 2.31±0.19 b/min/mmHg in SHR-S). These responses were followed by increased vagal component of heart rate variability (1.9-fold) and resting bradycardia (−13%) at the 4th week, and, by reduced vasomotor component of pressure variability (−28%) and decreased mean arterial pressure (−7%) only at the 8th week of training. Our findings indicate that independent of the high pressure levels in SHR, training promptly restores baroreflex function by disrupting the positive feedback between high oxidative stress and increased pro-inflammatory cytokines secretion within the hypothalamic paraventricular nucleus. These early adaptive responses precede the occurrence of training-induced resting bradycardia and blood pressure fall.
Collapse
|
|
42
|
Kenkel WM, Suboc G, Carter CS. Autonomic, behavioral and neuroendocrine correlates of paternal behavior in male prairie voles. Physiol Behav 2014; 128:252-9. [PMID: 24534169 PMCID: PMC3988699 DOI: 10.1016/j.physbeh.2014.02.006] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2013] [Revised: 11/21/2013] [Accepted: 02/04/2014] [Indexed: 12/21/2022]
Abstract
Socially monogamous prairie voles (Microtus ochrogaster) are biparental and alloparental. In the present study, we compared behavioral, cardiovascular and neuroendocrine parameters in male prairie voles with experience caring for pups (Fathers), versus reproductively inexperienced Virgin males. Father and Virgins showed generally similar responses to unrelated pups. However, in the Fathers studied prior to and during pup exposure, heart rate was lower and respiratory sinus arrhythmia tended to be higher than that in Virgins. Fathers also displayed comparatively lower levels of anxiety-related behaviors in an open field test. In Fathers, compared to Virgin males, we also found higher levels of oxytocin-immunoreactivity in the paraventricular hypothalamus and two brainstem regions involved in the autonomic regulation of the heart--the nucleus ambiguus and nucleus tractus solitarius. However, Fathers had less oxytocin in the bed nucleus of the stria terminalis. Vasopressin did not differ significantly in these regions. Fathers also weighed less and had less subcutaneous fat and larger testes as a percentage of bodyweight. In conjunction with earlier findings in this species, the present study supports the hypothesis that oxytocin may be involved in the adaptation to fatherhood. These findings also support the hypothesis that males, with or without prior pup experience, may show simultaneous patterns of behavioral nurturance and autonomic states compatible with mobilization and vigilance.
Collapse
Affiliation(s)
- William M Kenkel
- Brain and Body Center, Dept. of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, United States.
| | - Gessa Suboc
- Brain and Body Center, Dept. of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, United States
| | - C Sue Carter
- Brain and Body Center, Dept. of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, United States
| |
Collapse
|
|
43
|
Wsol A, Szczepanska-Sadowska E, Kowalewski S, Puchalska L, Cudnoch-Jedrzejewska A. Oxytocin differently regulates pressor responses to stress in WKY and SHR rats: the role of central oxytocin and V1a receptors. Stress 2014; 17:117-25. [PMID: 24308490 DOI: 10.3109/10253890.2013.872620] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The role of central oxytocin in the regulation of cardiovascular parameters under resting conditions and during acute stress was investigated in male normotensive Wistar-Kyoto (WKY; n = 40) and spontaneously hypertensive rats (SHR; n = 28). In Experiment 1, mean arterial blood pressure (MABP) and heart rate (HR) were recorded in WKY and SHR rats at rest and after an air-jet stressor during intracerebroventricular (ICV) infusions of vehicle, oxytocin or oxytocin receptor (OTR) antagonist. In Experiment 2, the effects of vehicle, oxytocin and OTR antagonist were determined in WKY rats after prior administration of a V1a vasopressin receptor (V1aR) antagonist. Resting MABP and HR were not affected by any of the ICV infusions either in WKY or in SHR rats. In control experiments (vehicle), the pressor response to stress was significantly higher in SHR. Oxytocin enhanced the pressor response to stress in the WKY rats but reduced it in SHR. During V1aR blockade, oxytocin infusion entirely abolished the pressor response to stress in WKY rats. Combined blockade of V1aR and OTR elicited a significantly greater MABP response to stress than infusion of V1a antagonist and vehicle. This study reveals significant differences in the regulation of blood pressure in WKY and SHR rats during alarming stress. Specifically, the augmentation of the pressor response to stress by exogenous oxytocin in WKY rats is caused by its interaction with V1aR, and endogenous oxytocin regulates the magnitude of the pressor response to stress in WKY rats by simultaneous interaction with OTR and V1aR.
Collapse
Affiliation(s)
- A Wsol
- Department of Experimental and Clinical Physiology, Medical University of Warsaw , Warsaw , Poland
| | | | | | | | | |
Collapse
|
|
44
|
Chies AB, Rossignoli PDS, Baptista RDFF, de Lábio RW, Payão SLM. Exercise reduces angiotensin II responses in rat femoral veins. Peptides 2013; 44:47-54. [PMID: 23528515 DOI: 10.1016/j.peptides.2013.01.020] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2012] [Revised: 01/31/2013] [Accepted: 01/31/2013] [Indexed: 11/20/2022]
Abstract
The control of blood flow during exercise involves different mechanisms, one of which is the activation of the renin-angiotensin system, which contributes to exercise-induced blood flow redistribution. Moreover, although angiotensin II (Ang II) is considered a potent venoconstrictor agonist, little is known about its effects on the venous bed during exercise. Therefore, the present study aimed to assess the Ang II responses in the femoral vein taken from sedentary and trained rats at rest or subjected to a single bout of exercise immediately before organ bath experiments. Isolated preparations of femoral veins taken from resting-sedentary, exercised-sedentary, resting-trained and exercised-trained animals were studied in an organ bath. In parallel, the mRNA expression of prepro-endothelin-1 (ppET-1), as well as the ETA and ETB receptors, was quantified by real-time PCR in this tissue. The results show that, in the presence of L-NAME, Ang II responses in resting-sedentary animals were higher compared to the other groups. However, this difference disappeared after co-treatment with indomethacin, BQ-123 or BQ-788. Moreover, exercise reduced ppET-1 mRNA expression. These reductions in mRNA expression were more evident in resting-trained animals. In conclusion, either acute or repeated exercise adapts the rat femoral veins, thereby reducing the Ang II responses. This adaptation is masked by the action of locally produced nitric oxide and involves, at least partially, the ETB- mediated release of vasodilator prostanoids. Reductions in endothelin-1 production may also be involved in these exercise-induced modifications of Ang II responses in the femoral vein.
Collapse
|
|
45
|
Moghimian M, Faghihi M, Karimian SM, Imani A, Houshmand F, Azizi Y. Role of central oxytocin in stress-induced cardioprotection in ischemic-reperfused heart model. J Cardiol 2012; 61:79-86. [PMID: 23159205 DOI: 10.1016/j.jjcc.2012.08.021] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2012] [Revised: 06/23/2012] [Accepted: 08/06/2012] [Indexed: 01/01/2023]
Abstract
BACKGROUND AND PURPOSE There is growing evidence that stress contributes to cardiovascular disease and triggers the release of oxytocin. Moreover previous studies confirmed oxytocin mimics the protection associated with ischemic preconditioning. The present study was aimed to assess the possible cardioprotective effects of the centrally released oxytocin in response to stress and intracerebroventricular (i.c.v.) administration of exogenous oxytocin in ischemic-reperfused isolated rat heart. METHODS AND SUBJECTS Rats were divided in two main groups and all of them were subjected to i.c.v. infusion of vehicle or drugs: unstressed rats [control: vehicle, oxytocin (OT; 100 ng/5 μl), atosiban (ATO; 4.3 μg/5 μl) as oxytocin antagonist, ATO+OT] and stressed rats [St: stress, OT+St, ATO+St]. After anesthesia, hearts were isolated and subjected to 30 min regional ischemia and 60 min reperfusion (IR). Acute stress protocol included swimming for 10 min before anesthesia. Myocardial function, infarct size, coronary flow, ventricular arrhythmia, and biochemical parameters such as creatine kinase and lactate dehydrogenase were measured. Ischemia-induced ventricular arrhythmias were counted during the occlusion period. RESULTS The plasma levels of oxytocin and corticosterone were significantly elevated by stress. Unexpectedly hearts of stressed rats showed a marked depression of IR injury compared to control group. I.c.v. infusion of oxytocin mimicked the cardioprotective effects of stress, yet did not elevate plasma oxytocin level. The protective effects of both stress and i.c.v. oxytocin were blocked by i.c.v. oxytocin antagonist. CONCLUSIONS These findings suggest that i.c.v. infusion of exogenous oxytocin and centrally released endogenous oxytocin in response to stress could play a role in induction of a preconditioning effect in ischemic-reperfused rat heart via brain receptors.
Collapse
Affiliation(s)
- Maryam Moghimian
- Department of Physiology, School of Medicine, Gonabad University of Medical Science, Gonabad, Islamic Republic of Iran
| | | | | | | | | | | |
Collapse
|
|
46
|
Cruz JC, Cavalleri MT, Ceroni A, Michelini LC. Peripheral chemoreceptors mediate training-induced plasticity in paraventricular nucleus pre-autonomic oxytocinergic neurons. Exp Physiol 2012; 98:386-96. [DOI: 10.1113/expphysiol.2012.065888] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
|
|
47
|
Onaka T, Takayanagi Y, Yoshida M. Roles of oxytocin neurones in the control of stress, energy metabolism, and social behaviour. J Neuroendocrinol 2012; 24:587-98. [PMID: 22353547 DOI: 10.1111/j.1365-2826.2012.02300.x] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Oxytocin neurones are activated by stressful stimuli, food intake and social attachment. Activation of oxytocin neurones in response to stressful stimuli or food intake is mediated, at least in part, by noradrenaline/prolactin-releasing peptide (PrRP) neurones in the nucleus tractus solitarius, whereas oxytocin neurones are activated after social stimuli via medial amygdala neurones. Activation of oxytocin neurones induces the release of oxytocin not only from their axon terminals, but also from their dendrites. Oxytocin acts locally where released or diffuses and acts on remote oxytocin receptors widely distributed within the brain, resulting in anxiolytic, anorexic and pro-social actions. The action sites of oxytocin appear to be multiple. Oxytocin shows anxiolytic actions, at least in part, via serotoninergic neurones in the median raphe nucleus, has anorexic actions via pro-opiomelanocortin neurones in the nucleus tractus solitarius and facilitates social recognition via the medial amygdala. Stress, obesity and social isolation are major risk factors for mortality in humans. Thus, the oxytocin-oxytocin receptor system is a therapeutic target for the promotion of human health.
Collapse
Affiliation(s)
- T Onaka
- Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University, Shinotsuke-shi, Tochigi-ken, Japan.
| | | | | |
Collapse
|
|
48
|
Kubzansky LD, Mendes WB, Appleton AA, Block J, Adler GK. A heartfelt response: Oxytocin effects on response to social stress in men and women. Biol Psychol 2012; 90:1-9. [PMID: 22387929 DOI: 10.1016/j.biopsycho.2012.02.010] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2011] [Revised: 01/25/2012] [Accepted: 02/15/2012] [Indexed: 11/18/2022]
Abstract
BACKGROUND Animal research indicates that oxytocin is involved in social behavior, stress regulation, and positive physiologic adaptation. This study examines whether oxytocin enhances adaptive responses to social stress and compares effects between men and women. METHODS Hypotheses were tested with a placebo-controlled, double-blind experiment. Social stress was induced. Changes in cardiovascular reactivity, affect, and behavior were assessed. RESULTS Participants given oxytocin, relative to placebo, responded to social stress with a challenge orientation characterized by a benign pattern of cardiovascular reactivity. Gender differences emerged. Men given oxytocin reported less negative affect and had greater vagal rebound, while women given oxytocin reported more anger and had better math performance following social stress. DISCUSSION Findings indicate oxytocin stimulates an approach-oriented cardiovascular profile during social stress, suggesting mechanisms by which oxytocin might improve physical health. However, before considering oxytocin as therapeutic or uniformly enhancing health, greater understanding of possible gender differences in effects is needed.
Collapse
Affiliation(s)
- Laura D Kubzansky
- Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA 02115, USA.
| | | | | | | | | |
Collapse
|
|
49
|
Stern JE, Sonner PM, Son SJ, Silva FCP, Jackson K, Michelini LC. Exercise training normalizes an increased neuronal excitability of NTS-projecting neurons of the hypothalamic paraventricular nucleus in hypertensive rats. J Neurophysiol 2012; 107:2912-21. [PMID: 22357793 DOI: 10.1152/jn.00884.2011] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Elevated sympathetic outflow and altered autonomic reflexes, including impaired baroreflex function, are common findings observed in hypertensive disorders. Although a growing body of evidence supports a contribution of preautonomic neurons in the hypothalamic paraventricular nucleus (PVN) to altered autonomic control during hypertension, the precise underlying mechanisms remain unknown. Here, we aimed to determine whether the intrinsic excitability and repetitive firing properties of preautonomic PVN neurons that innervate the nucleus tractus solitarii (PVN-NTS neurons) were altered in spontaneously hypertensive rats (SHR). Moreover, given that exercise training is known to improve and/or correct autonomic deficits in hypertensive conditions, we evaluated whether exercise is an efficient behavioral approach to correct altered neuronal excitability in hypertensive rats. Patch-clamp recordings were obtained from retrogradely labeled PVN-NTS neurons in hypothalamic slices obtained from sedentary (S) and trained (T) Wistar-Kyoto (WKY) and SHR rats. Our results indicate an increased excitability of PVN-NTS neurons in SHR-S rats, reflected by an enhanced input-output function in response to depolarizing stimuli, a hyperpolarizing shift in Na(+) spike threshold, and smaller hyperpolarizing afterpotentials. Importantly, we found exercise training in SHR rats to restore all these parameters back to those levels observed in WKY-S rats. In several cases, exercise evoked opposing effects in WKY-S rats compared with SHR-S rats, suggesting that exercise effects on PVN-NTS neurons are state dependent. Taken together, our results suggest that elevated preautonomic PVN-NTS neuronal excitability may contribute to altered autonomic control in SHR rats and that exercise training efficiently corrects these abnormalities.
Collapse
Affiliation(s)
- Javier E Stern
- Dept. of Physiology, Georgia Health Sciences Univ., Augusta, GA 30912, USA.
| | | | | | | | | | | |
Collapse
|
|
50
|
Amaral S, Michelini L. Effect of gender on training-induced vascular remodeling in SHR. Braz J Med Biol Res 2011; 44:814-26. [DOI: 10.1590/s0100-879x2011007500055] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2011] [Accepted: 04/13/2011] [Indexed: 02/07/2023] Open
Affiliation(s)
- S.L. Amaral
- Universidade, Brasil; Universidade Federal de São Carlos, Brasil
| | | |
Collapse
|