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For: Fu Q, Zhang R, Witkowski S, Arbab-Zadeh A, Prasad A, Okazaki K, Levine BD. Persistent sympathetic activation during chronic antihypertensive therapy: a potential mechanism for long term morbidity? Hypertension 2005;45:513-21. [PMID: 15738344 DOI: 10.1161/01.hyp.0000158312.63381.c1] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]

For:	Fu Q, Zhang R, Witkowski S, Arbab-Zadeh A, Prasad A, Okazaki K, Levine BD. Persistent sympathetic activation during chronic antihypertensive therapy: a potential mechanism for long term morbidity? Hypertension 2005;45:513-21. [PMID: 15738344 DOI: 10.1161/01.hyp.0000158312.63381.c1] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]

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Cited by Other Article(s)

Quarti-Trevano F, Seravalle G, Facchetti R, Tsioufis K, Dimitriadis K, Manta E, Mancia G, Grassi G. Failure of Antihypertensive Treatment to Restore Normal Sympathetic Activity. Hypertension 2025;82:1024-1034. [PMID: 40367218 DOI: 10.1161/hypertensionaha.124.24429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 04/01/2025] [Indexed: 05/16/2025]

Abstract

BACKGROUND

Sympathetic deactivation represents a major goal of antihypertensive drug treatment. However, whether treatment normalizes the hypertension-related sympathetic cardiovascular overdrive remains uncertain.

METHODS

In 219 middle-aged essential hypertensives, we analyzed, along with office systolic and diastolic blood pressure (BP) and heart rate, muscle sympathetic nerve traffic (MSNA, microneurography) before and after 3-month treatment, either as monotherapy or as combination. Controls were represented by 100 age-matched normotensives.

RESULTS

Treatment caused, along with a small heart rate decrease, a clear BP reduction (from 160.5/95.5 to 142.3/85.0 mm Hg, P<0.01) and a significant MSNA inhibition (from 70.7±11.5 to 65.0±10.2 bursts/100 heartbeats, mean±SD, P<0.01). A similar pattern was detected in patients under monotherapy (n=81) or combination drug treatment (n=138). MSNA was significantly related to systolic BP before and during treatment but unrelated to heart rate. In treated patients achieving the lower BP (135.1/84.5 mm Hg, n=90), the MSNA reduction was greater than that detected in patients with the higher on-treatment BP (146.7/87.4 mm Hg, n=129). However, even in patients achieving a BP target <140/90 mm Hg, MSNA remained markedly higher (on average +66.4%) compared with controls. This was the case even when treated BP was <130/80 mm Hg. Data were similar for different antihypertensive drug classes.

CONCLUSIONS

Thus, antihypertensive treatment, even when effective in achieving BP control, fails to restore the level of normotension-related MSNA, with a persistence of the pattern of heightened sympathetic influences typical of untreated patients with hypertension. Failure of normalization may contribute to the development of the residual cardiovascular risk reported in treated hypertensives.

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Smith EC, Patel JN, Wahba A, Cluckey A, Celedonio J, Park J, Hannah L, Lonce S, Shibao CA, Paranjape SY, Diedrich A, McGuinness O, Wasserman DH, Biaggioni I, Gamboa A. Acute Sympathetic Blockade Improves Insulin-Mediated Microvascular Blood Flow in the Forearm of Adult Human Subjects With Obesity. J Am Heart Assoc 2024;13:e030775. [PMID: 39119951 PMCID: PMC11963928 DOI: 10.1161/jaha.123.030775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 06/05/2024] [Indexed: 08/10/2024]

Abstract

BACKGROUND

Obesity is associated with resistance to the metabolic (glucose uptake) and vascular (nitric-oxide mediated dilation and microvascular recruitment) actions of insulin. These vascular effects contribute to insulin sensitivity by increasing tissue delivery of glucose. Studies by us and others suggest that sympathetic activation contributes to insulin resistance to glucose uptake. Here we tested the hypothesis that sympathetic activation contributes to impaired insulin-mediated vasodilation in adult subjects with obesity.

METHODS AND RESULTS

In a randomized crossover study, we used a euglycemic hyperinsulinemic clamp in 12 subjects with obesity to induce forearm arterial vasodilation (forearm blood flow) and microvascular recruitment (contrast-enhanced ultrasonography) during an intrabrachial infusion of saline (control) or phentolamine (sympathetic blockade). Insulin increased forearm blood flow on both study days (from 2.21±1.22 to 4.89±4.21 mL/100 mL per min, P=0.003 and from 2.42±0.89 to 7.19±3.35 mL/100 mL per min, P=0.002 for the intact and blocked day, respectively). Sympathetic blockade with phentolamine resulted in a significantly greater increase in microvascular flow velocity (∆microvascular flow velocity: 0.23±0.65 versus 2.51±3.01 arbitrary intensity units (AIU/s) for saline and phentolamine respectively, P=0.005), microvascular blood volume (∆microvascular blood volume: 1.69±2.45 versus 3.76±2.93 AIU, respectively, P=0.05), and microvascular blood flow (∆microvascular blood flow: 0.28±0.653 versus 2.51±3.01 AIU2/s, respectively, P=0.0161). To evaluate if this effect was not due to nonspecific vasodilation, we replicated the study in 6 subjects with obesity comparing intrabrachial infusion of phentolamine to sodium nitroprusside. At doses that produced similar increases in forearm blood flow, insulin-induced changes in microvascular flow velocity were greater during phentolamine than sodium nitroprusside (%microvascular flow velocity=58% versus 29%, respectively, P=0.031).

CONCLUSIONS

We conclude that sympathetic activation impairs insulin-mediated microvascular recruitment in adult subjects with obesity.

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Ikeda S, Shinohara K, Kashihara S, Matsumoto S, Yoshida D, Nakashima R, Ono Y, Matsushima S, Tsutsui H, Kinugawa S. Esaxerenone: blood pressure reduction and cardiorenal protection without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats. Hypertens Res 2024;47:2133-2143. [PMID: 38802501 DOI: 10.1038/s41440-024-01733-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 04/18/2024] [Accepted: 05/07/2024] [Indexed: 05/29/2024]

Abstract

Mineralocorticoid receptor (MR) is involved in the mechanisms of blood pressure elevation, organ fibrosis, and inflammation. MR antagonists have been used in patients with hypertension, heart failure, or chronic kidney disease. Esaxerenone, a recently approved MR blocker with a nonsteroidal structure, has demonstrated a strong blood pressure-lowering effect. However, blood pressure reduction may lead to sympathetic activation through the baroreflex. The effect of esaxerenone on the sympathetic nervous system remains unclear. We investigated the effect of esaxerenone on organ damage and the sympathetic nervous system in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP), a well-established model of essential hypertension with sympathoexcitation and organ damage. Three-week administration of esaxerenone or hydralazine successfully attenuated the blood pressure elevation. Both esaxerenone and hydralazine comparably suppressed left ventricular hypertrophy and urinary albumin excretion. However, renal fibrosis and glomerular sclerosis were suppressed by esaxerenone but not hydralazine. Furthermore, plasma norepinephrine level, a parameter of systemic sympathetic activity, was significantly increased by hydralazine but not by esaxerenone. Consistent with these findings, the activity of the control centers of sympathetic nervous system, the parvocellular region of the paraventricular nucleus in the hypothalamus and the rostral ventrolateral medulla, was enhanced by hydralazine but remained unaffected by esaxerenone. These results suggest that esaxerenone effectively lowers blood pressure without inducing reflex sympathetic nervous system activation. Moreover, the organ-protective effects of esaxerenone appear to be partially independent of its blood pressure-lowering effect. In conclusion, esaxerenone demonstrates a blood pressure-lowering effect without concurrent sympathetic activation and exerts organ-protective effects in salt-loaded SHRSP. Esaxerenone has antihypertensive and cardiorenal protective effects without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats.

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Affiliation(s)

Shota Ikeda Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
Keisuke Shinohara Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan. Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
Soichiro Kashihara Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
Sho Matsumoto Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
Daisuke Yoshida Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
Ryosuke Nakashima Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
Yoshiyasu Ono Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
Shouji Matsushima Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan
Hiroyuki Tsutsui Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan School of Medicine and Graduate School, International University of Health and Welfare, Fukuoka, Japan
Shintaro Kinugawa Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan Division of Cardiovascular Medicine, Research Institute of Angiocardiology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan

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Grassi G. Sympathetic modulation as a goal of antihypertensive treatment: from drugs to devices. J Hypertens 2023;41:1688-1695. [PMID: 37602470 PMCID: PMC10552843 DOI: 10.1097/hjh.0000000000003538] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 07/26/2023] [Accepted: 07/28/2023] [Indexed: 08/22/2023]

Abidi AM, Mujaddadi A, Raza S, Moiz JA. Effect of Physical Exercise on Cardiac Autonomic Modulation in Hypertensive Individuals: A Systematic Review and Meta-analysis. Curr Hypertens Rev 2023;19:149-172. [PMID: 37563821 DOI: 10.2174/1573402119666230803090330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 07/10/2023] [Accepted: 07/10/2023] [Indexed: 08/12/2023]

Abstract

BACKGROUND

Cardiac autonomic dysfunction is associated with hypertension and exercise training (ET) in healthy individuals is found to improve cardiac autonomic modulation (CAM). However, the effects of physical exercise on CAM in hypertensive individuals are under debate.

OBJECTIVE

The aim of the review is to systematically evaluate the literature on the effects of physical exercise on CAM in hypertensive individuals and analyse comparative differences in the effects of exercise between hypertensive and normotensive individuals.

METHODS

Electronic databases, such as Pubmed, PEDro, Scopus, and Web of Science, were systematically searched from inception up to February, 2022, evaluating the effect of ET on CAM either by heart rate variability (HRV), baroreflex sensitivity or heart rate recovery. Fifteen studies were included in the review. The risk of bias was assessed using the Cochrane risk of bias tool version 2 and the risk of bias in studies of intervention (ROBINS-I) tool. The overall quality of evidence was assessed using the grading of recommendations, assessment, development, and evaluation approach. Ten studies were included in the quantitative analysis. The meta-analysis and sensitivity analysis were performed using review manager 5.4.1; publication bias was assessed using Jamovi 2.2.5 software.

RESULTS

The qualitative analysis revealed low to moderate certainty of evidence for ET and moderate for aerobic training. For the effect of overall ET, the analysis revealed that the standardized mean differences (SMD) showed a significant effect of ET on HF (SMD 1.76, p = 0.04) and RMSSD (SMD 1.19, p < 0.0001) and a significant decrease in LF (SMD -1.78, p = 0.04). Aerobic training revealed nonsignificant improvement in HRV parameters. In the comparative analysis, ET did not show a significant difference in improvement between hypertensive and normotensive individuals.

CONCLUSION

This review suggests an improvement in CAM with physical exercise in hypertensive individuals, but the overall effect of ET in hypertensive individuals must be interpreted with caution as the robustness of the data is compromised in the sensitivity analysis of the trials. High-quality future trials focusing on different modes of ET interventions are needed to strengthen the findings of the present review.

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Sailer C, Edelmann H, Buchanan C, Giro P, Babcock M, Swanson C, Spotts M, Schulte M, Pratt-Cordova A, Coe G, Beindorff M, Page RL, Ambardekar AV, Pal JD, Kohrt W, Wolfel E, Lawley JS, Tarumi T, Cornwell WK. Impairments in Blood Pressure Regulation and Cardiac Baroreceptor Sensitivity Among Patients With Heart Failure Supported With Continuous-Flow Left Ventricular Assist Devices. Circ Heart Fail 2021;14:e007448. [PMID: 33464953 DOI: 10.1161/circheartfailure.120.007448] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]

Abstract

BACKGROUND

Continuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse predisposes to side-effects including uncontrolled blood pressure (BP), and there are little data regarding the impact of CF-LVADs on BP regulation.

METHODS

Twelve patients (10 males, 60±11 years) with advanced heart failure completed hemodynamic assessment 2.7±4.1 months before, and 4.3±1.3 months following CF-LVAD implantation. Heart rate and systolic BP via arterial catheterization were monitored during Valsalva maneuver, spontaneous breathing, and a 0.05 Hz repetitive squat-stand maneuver to characterize cardiac baroreceptor sensitivity. Plasma norepinephrine levels were assessed during head-up tilt at supine, 30^o and 60^o. Heart rate and BP were monitored during cardiopulmonary exercise testing.

RESULTS

Cardiac baroreceptor sensitivity, determined by Valsalva as well as Fourier transformation and transfer function gain of Heart rate and systolic BP during spontaneous breathing and squat-stand maneuver, was impaired before and following LVAD implantation. Norepinephrine levels were markedly elevated pre-LVAD and improved-but remained elevated post-LVAD (supine norepinephrine pre-LVAD versus post-LVAD: 654±437 versus 323±164 pg/mL). BP increased during cardiopulmonary exercise testing post-LVAD, but the magnitude of change was modest and comparable to the changes observed during the pre-LVAD cardiopulmonary exercise testing.

CONCLUSIONS

Among patients with advanced heart failure with reduced ejection fraction, CF-LVAD implantation is associated with modest improvements in autonomic tone, but persistent reductions in cardiac baroreceptor sensitivity. Exercise-induced increases in BP are blunted. These findings shed new light on mechanisms for adverse events such as stroke, and persistent reductions in functional capacity, among patients supported by CF-LVADs. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078972.

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Affiliation(s)

Christine Sailer Department of Medicine-Cardiology (C.S., G.C., M.B., A.V.A., E.W., W.K.C.), University of Colorado Anschutz Medical Campus, Aurora
Hannah Edelmann University of Colorado-Denver (H.E.)
Cullen Buchanan Department of Medicine (C.B., P.G.), University of Colorado Anschutz Medical Campus, Aurora
Pedro Giro Department of Medicine (C.B., P.G.), University of Colorado Anschutz Medical Campus, Aurora
Matthew Babcock Division of Geriatric Medicine, Department of Medicine (M.B., W.K.), University of Colorado Anschutz Medical Campus, Aurora
Christine Swanson Department of Medicine-Endocrinology, Metabolism and Diabetes (C.S.), University of Colorado Anschutz Medical Campus, Aurora
Melanie Spotts Clinical and Translational Research Center (M. Spotts, M. Schulte, A.P.-C., W.K., W.K.C.), University of Colorado Anschutz Medical Campus, Aurora
Margaret Schulte Clinical and Translational Research Center (M. Spotts, M. Schulte, A.P.-C., W.K., W.K.C.), University of Colorado Anschutz Medical Campus, Aurora
Ashley Pratt-Cordova Clinical and Translational Research Center (M. Spotts, M. Schulte, A.P.-C., W.K., W.K.C.), University of Colorado Anschutz Medical Campus, Aurora
Greg Coe Department of Medicine-Cardiology (C.S., G.C., M.B., A.V.A., E.W., W.K.C.), University of Colorado Anschutz Medical Campus, Aurora
Mark Beindorff Department of Medicine-Cardiology (C.S., G.C., M.B., A.V.A., E.W., W.K.C.), University of Colorado Anschutz Medical Campus, Aurora
Robert L Page Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Services, Aurora (R.L.P.)
Amrut V Ambardekar Department of Medicine-Cardiology (C.S., G.C., M.B., A.V.A., E.W., W.K.C.), University of Colorado Anschutz Medical Campus, Aurora
Jay D Pal Department of Cardiothoracic Surgery (J.D.P.), University of Colorado Anschutz Medical Campus, Aurora
Wendy Kohrt Division of Geriatric Medicine, Department of Medicine (M.B., W.K.), University of Colorado Anschutz Medical Campus, Aurora.,Clinical and Translational Research Center (M. Spotts, M. Schulte, A.P.-C., W.K., W.K.C.), University of Colorado Anschutz Medical Campus, Aurora
Eugene Wolfel Department of Medicine-Cardiology (C.S., G.C., M.B., A.V.A., E.W., W.K.C.), University of Colorado Anschutz Medical Campus, Aurora
Justin S Lawley Department of Sport Science, University of Innsbruck, Austria (J.S.L.)
Takashi Tarumi Human Informatics Interaction Research Institute, National Institute of Advanced Industrial Science and Technology, Ibaraki prefecture, Japan (T.T.)
William K Cornwell Department of Medicine-Cardiology (C.S., G.C., M.B., A.V.A., E.W., W.K.C.), University of Colorado Anschutz Medical Campus, Aurora.,Clinical and Translational Research Center (M. Spotts, M. Schulte, A.P.-C., W.K., W.K.C.), University of Colorado Anschutz Medical Campus, Aurora

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Nardone M, Floras JS, Millar PJ. Sympathetic neural modulation of arterial stiffness in humans. Am J Physiol Heart Circ Physiol 2020;319:H1338-H1346. [PMID: 33035441 DOI: 10.1152/ajpheart.00734.2020] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]

Haspula D, Clark MA. Neuroinflammation and sympathetic overactivity: Mechanisms and implications in hypertension. Auton Neurosci 2018;210:10-17. [DOI: 10.1016/j.autneu.2018.01.002] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Revised: 01/02/2018] [Accepted: 01/08/2018] [Indexed: 02/07/2023]

Jordan J, Tank J, Heusser K, Heise T, Wanner C, Heer M, Macha S, Mattheus M, Lund SS, Woerle HJ, Broedl UC. The effect of empagliflozin on muscle sympathetic nerve activity in patients with type II diabetes mellitus. ACTA ACUST UNITED AC 2017;11:604-612. [PMID: 28757109 DOI: 10.1016/j.jash.2017.07.005] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Revised: 07/07/2017] [Accepted: 07/12/2017] [Indexed: 11/16/2022]

Notay K, Incognito AV, Millar PJ. Acute beetroot juice supplementation on sympathetic nerve activity: a randomized, double-blind, placebo-controlled proof-of-concept study. Am J Physiol Heart Circ Physiol 2017;313:H59-H65. [DOI: 10.1152/ajpheart.00163.2017] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 05/03/2017] [Accepted: 05/03/2017] [Indexed: 01/09/2023]

Abstract Acute dietary nitrate ([Formula: see text]) supplementation reduces resting blood pressure in healthy normotensives. This response has been attributed to increased nitric oxide bioavailability and peripheral vasodilation, although nitric oxide also tonically inhibits central sympathetic outflow. We hypothesized that acute dietary [Formula: see text] supplementation using beetroot (BR) juice would reduce blood pressure and muscle sympathetic nerve activity (MSNA) at rest and during exercise. Fourteen participants (7 men and 7 women, age: 25 ± 10 yr) underwent blood pressure and MSNA measurements before and after (165–180 min) ingestion of 70ml high-[Formula: see text] (~6.4 mmol [Formula: see text]) BR or [Formula: see text]-depleted BR placebo (PL; ~0.0055 mmol [Formula: see text]) in a double-blind, randomized, crossover design. Blood pressure and MSNA were also collected during 2 min of static handgrip (30% maximal voluntary contraction). The changes in resting MSNA burst frequency (−3 ± 5 vs. 3 ± 4 bursts/min, P = 0.001) and burst incidence (−4 ± 7 vs. 4 ± 5 bursts/100 heart beats, P = 0.002) were lower after BR versus PL, whereas systolic blood pressure (−1 ± 5 vs. 2 ± 5 mmHg, P = 0.30) and diastolic blood pressure (4 ± 5 vs. 5 ± 7 mmHg, P = 0.68) as well as spontaneous arterial sympathetic baroreflex sensitivity ( P = 0.95) were not different. During static handgrip, the change in MSNA burst incidence (1 ± 8 vs. 8 ± 9 bursts/100 heart beats, P = 0.04) was lower after BR versus PL, whereas MSNA burst frequency (6 ± 6 vs. 11 ± 10 bursts/min, P = 0.11) as well as systolic blood pressure (11 ± 7 vs. 12 ± 8 mmHg, P = 0.94) and diastolic blood pressure (11 ± 4 vs. 11 ± 4 mmHg, P = 0.60) were not different. Collectively, these data provide proof of principle that acute BR supplementation can decrease central sympathetic outflow at rest and during exercise. Dietary [Formula: see text] supplementation may represent a novel intervention to target exaggerated sympathetic outflow in clinical populations. NEW & NOTEWORTHY The hemodynamic benefits of dietary nitrate supplementation have been attributed to nitric oxide-mediated peripheral vasodilation. Here, we provide proof of concept that acute dietary nitrate supplementation using beetroot juice can decrease muscle sympathetic outflow at rest and during exercise in a normotensive population. These results have applications for targeting central sympathetic overactivation in disease. Collapse

Howden EJ, East C, Lawley JS, Stickford AS, Verhees M, Fu Q, Levine BD. Integrative Blood Pressure Response to Upright Tilt Post Renal Denervation. Am J Hypertens 2017;30:632-641. [PMID: 28338768 DOI: 10.1093/ajh/hpx018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 02/03/2017] [Indexed: 12/26/2022] Open

Howden EJ, Lawley JS, Esler M, Levine BD. Potential role of endurance training in altering renal sympathetic nerve activity in CKD? Auton Neurosci 2016;204:74-80. [PMID: 27908698 DOI: 10.1016/j.autneu.2016.11.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Revised: 11/16/2016] [Accepted: 11/23/2016] [Indexed: 12/20/2022]

Hildebrandt DA, Irwin ED, Lohmeier TE. Prolonged Baroreflex Activation Abolishes Salt-Induced Hypertension After Reductions in Kidney Mass. Hypertension 2016;68:1400-1406. [PMID: 27777356 DOI: 10.1161/hypertensionaha.116.08293] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Revised: 09/04/2016] [Accepted: 09/28/2016] [Indexed: 12/20/2022]

Jarvis SS, Okada Y, Levine BD, Fu Q. Central integration and neural control of blood pressure during the cold pressor test: a comparison between hydrochlorothiazide and aliskiren. Physiol Rep 2015;3:3/9/e12502. [PMID: 26465969 PMCID: PMC4600375 DOI: 10.14814/phy2.12502] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Accepted: 07/21/2015] [Indexed: 02/07/2023] Open

Iliescu R, Lohmeier TE, Tudorancea I, Laffin L, Bakris GL. Renal denervation for the treatment of resistant hypertension: review and clinical perspective. Am J Physiol Renal Physiol 2015. [PMID: 26224718 DOI: 10.1152/ajprenal.00246.2015] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open

Bhatt H, Safford M, Stephen G. Coronary heart disease risk factors and outcomes in the twenty-first century: findings from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Curr Hypertens Rep 2015;17:541. [PMID: 25794955 PMCID: PMC4443695 DOI: 10.1007/s11906-015-0541-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]

Lohmeier TE, Iliescu R. The baroreflex as a long-term controller of arterial pressure. Physiology (Bethesda) 2015;30:148-58. [PMID: 25729060 PMCID: PMC4346703 DOI: 10.1152/physiol.00035.2014] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open

Best SA, Bivens TB, Dean Palmer M, Boyd KN, Melyn Galbreath M, Okada Y, Carrick-Ranson G, Fujimoto N, Shibata S, Hastings JL, Spencer MD, Tarumi T, Levine BD, Fu Q. Heart rate recovery after maximal exercise is blunted in hypertensive seniors. J Appl Physiol (1985) 2014;117:1302-7. [PMID: 25301897 DOI: 10.1152/japplphysiol.00395.2014] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open

Affiliation(s)

Stuart A Best Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and University of Texas Southwestern Medical Center, Dallas, Texas
Tiffany B Bivens Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and
M Dean Palmer Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and
Kara N Boyd Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and
M Melyn Galbreath Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and University of Texas Southwestern Medical Center, Dallas, Texas
Yoshiyuki Okada Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and University of Texas Southwestern Medical Center, Dallas, Texas
Graeme Carrick-Ranson Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and University of Texas Southwestern Medical Center, Dallas, Texas
Naoki Fujimoto Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and University of Texas Southwestern Medical Center, Dallas, Texas
Shigeki Shibata Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and University of Texas Southwestern Medical Center, Dallas, Texas
Jeffrey L Hastings Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and University of Texas Southwestern Medical Center, Dallas, Texas
Matthew D Spencer Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and University of Texas Southwestern Medical Center, Dallas, Texas
Takashi Tarumi Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and University of Texas Southwestern Medical Center, Dallas, Texas
Benjamin D Levine Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and University of Texas Southwestern Medical Center, Dallas, Texas
Qi Fu Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas; and University of Texas Southwestern Medical Center, Dallas, Texas

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Gronda E, Lovett EG, Tarascio M, Georgakopoulos D, Grassi G, Vanoli E. The baroreceptor as a therapeutic target for heart failure. J Cardiovasc Transl Res 2014;7:301-9. [PMID: 24563340 DOI: 10.1007/s12265-014-9546-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Accepted: 01/30/2014] [Indexed: 01/08/2023]

Okada Y, Jarvis SS, Best SA, Bivens TB, Adams-Huet B, Levine BD, Fu Q. Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors. J Physiol 2013;591:5913-22. [PMID: 24060993 DOI: 10.1113/jphysiol.2013.261362] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open

Abstract

Cardiovascular risk remains high in patients with hypertension even with adequate blood pressure (BP) control. One possible mechanism may be sympathetic activation via the baroreflex. We tested the hypothesis that chronic inhibition of renin reduces BP without sympathetic activation, but diuresis augments sympathetic activity in elderly hypertensives. Fourteen patients with stage-I hypertension (66 ± 5 (SD) years) were treated with a direct renin inhibitor, aliskiren (n = 7), or a diuretic, hydrochlorothiazide (n = 7), for 6 months. Muscle sympathetic nerve activity (MSNA), BP, direct renin and aldosterone were measured during supine and a graded head-up tilt (HUT; 5 min 30° and 20 min 60°), before and after treatment. Sympathetic baroreflex sensitivity (BRS) was assessed. Both groups had similar BP reductions after treatment (all P < 0.01), while MSNA responses were different between hydrochlorothiazide and aliskiren (P = 0.006 pre/post × drug). Both supine and upright MSNA became greater after hydrochlorothiazide treatment (supine, 72 ± 18 post vs. 64 ± 15 bursts (100 beats)(-1) pre; 60° HUT, 83 ± 10 vs. 78 ± 13 bursts (100 beats)(-1); P = 0.002). After aliskiren treatment, supine MSNA remained unchanged (69 ± 13 vs. 64 ± 8 bursts (100 beats)(-1)), but upright MSNA was lower (74 ± 15 vs. 85 ± 10 bursts (100 beats)(-1); P = 0.012 for pre/post × posture). Direct renin was greater after both treatments (both P < 0.05), while upright aldosterone was greater after hydrochlorothiazide only (P = 0.002). The change in upright MSNA by the treatment was correlated with the change of aldosterone (r = 0.74, P = 0.002). Upright sympathetic BRS remained unchanged after either treatment. Thus, chronic renin inhibition may reduce upright MSNA through suppressed renin activity, while diuresis may evoke sympathetic activation via the upregulated renin-angiotensin-aldosterone system, without changing intrinsic sympathetic baroreflex function in elderly hypertensive patients.

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Johnson BD, Joyner MJ. Carotid body denervation: too soon to get breathless about heart failure? J Am Coll Cardiol 2013;62:2431-2432. [PMID: 24013054 DOI: 10.1016/j.jacc.2013.08.718] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Revised: 08/05/2013] [Accepted: 08/13/2013] [Indexed: 10/26/2022]

Charach G, Shochat M, Argov O, Weintraub M, Charach L, Rabinovich A, Ayzenberg O, George J. Seasonal changes in blood pressure: Cardiac and cerebrovascular morbidity and mortality. World J Hypertens 2013;3:1-8. [DOI: 10.5494/wjh.v3.i1.1] [Citation(s) in RCA: 6] [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: 12/03/2012] [Revised: 01/10/2013] [Accepted: 01/24/2013] [Indexed: 02/06/2023] Open

Brinkmann J, Heusser K, Schmidt BM, Menne J, Klein G, Bauersachs J, Haller H, Sweep FC, Diedrich A, Jordan J, Tank J. Catheter-based renal nerve ablation and centrally generated sympathetic activity in difficult-to-control hypertensive patients: prospective case series. Hypertension 2012;60:1485-90. [PMID: 23045466 DOI: 10.1161/hypertensionaha.112.201186] [Citation(s) in RCA: 143] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Raheja P, Price A, Wang Z, Arbique D, Adams-Huet B, Auchus RJ, Vongpatanasin W. Spironolactone prevents chlorthalidone-induced sympathetic activation and insulin resistance in hypertensive patients. Hypertension 2012;60:319-25. [PMID: 22733474 DOI: 10.1161/hypertensionaha.112.194787] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]

Abstract

Recent studies from our laboratory indicate that chlorthalidone triggers persistent activation of the sympathetic nervous system and promotes insulin resistance in hypertensive patients, independent of serum potassium. Mechanisms underlying these adverse effects of chlorthalidone remain unknown, but increasing evidence in rodents suggests the role of angiotensin and aldosterone excess in inducing both sympathetic overactivity and insulin resistance. Accordingly, we conducted studies in 17 subjects with untreated stage 1 hypertension, measuring sympathetic nerve activity at baseline and after 12 weeks of chlorthalidone alone (25 mg/d), chlorthalidone plus spironolactone, and chlorthalidone plus irbesartan, using randomized crossover design. We found that chlorthalidone alone decreased 24-hour ambulatory blood pressure from 135±3/84±2 to 124±2/78±2 mm Hg and significantly increased sympathetic nerve activity from baseline (from 41±3 versus 49±4 bursts per minute; P<0.01). The addition of spironolactone to chlorthalidone returned sympathetic nerve activity value to baseline (42±3 bursts per minute; P>0.05), whereas the addition of irbesartan failed to alter the sympathetic nerve activity response to chlorthalidone in the same subjects (52±2 bursts per minute; P<0.01) despite a similar reduction in ambulatory blood pressure (121±2/75±2 and 121±2/75±2 mm Hg, respectively). Chlorthalidone alone also increased indices of insulin resistance, which was not observed when used in combination with spironolactone. In conclusion, our study demonstrates beneficial effects of spironolactone in attenuating both chlorthalidone-induced sympathetic activation and insulin resistance in humans, independent of blood pressure reduction. Because sympathetic overactivity and insulin resistance contribute to the poor prognosis in patients with cardiovascular disease, combination therapy of chlorthalidone with mineralocorticoid receptor antagonists may constitute a preferable regimen than chlorthalidone alone in hypertensive patients.

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Hart EC, Charkoudian N. Sympathetic neural mechanisms in human blood pressure regulation. Curr Hypertens Rep 2011;13:237-43. [PMID: 21293977 DOI: 10.1007/s11906-011-0191-1] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]

The sympathetic nervous system and blood pressure in humans: implications for hypertension. J Hum Hypertens 2011;26:463-75. [PMID: 21734720 DOI: 10.1038/jhh.2011.66] [Citation(s) in RCA: 189] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]

Lohmeier TE, Iliescu R. Chronic lowering of blood pressure by carotid baroreflex activation: mechanisms and potential for hypertension therapy. Hypertension 2011;57:880-6. [PMID: 21357283 PMCID: PMC3085950 DOI: 10.1161/hypertensionaha.108.119859] [Citation(s) in RCA: 79] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]

Kent ST, Howard G, Crosson WL, Prineas RJ, McClure LA. The association of remotely-sensed outdoor temperature with blood pressure levels in REGARDS: a cross-sectional study of a large, national cohort of African-American and white participants. Environ Health 2011;10:7. [PMID: 21247466 PMCID: PMC3032648 DOI: 10.1186/1476-069x-10-7] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2010] [Accepted: 01/19/2011] [Indexed: 05/02/2023]

Vongpatanasin W, Wang Z, Arbique D, Arbique G, Adams-Huet B, Mitchell JH, Victor RG, Thomas GD. Functional sympatholysis is impaired in hypertensive humans. J Physiol 2011;589:1209-20. [PMID: 21224235 DOI: 10.1113/jphysiol.2010.203026] [Citation(s) in RCA: 97] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open

Kobori H, Fu Q, Crowley SD, Gonzalez-Villalobos RA, Campos RR. Comments on Point:Counterpoint: The dominant contributor to systemic hypertension: Chronic activation of the sympathetic nervous system vs. Activation of the intrarenal renin-angiotensin system. Activated intrarenal renin-angiotensin system is correlated with high blood pressure in humans. J Appl Physiol (1985) 2010;109:2003. [PMID: 21148352 PMCID: PMC3774210 DOI: 10.1152/japplphysiol.01160.2010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open

Delaney EP, Greaney JL, Edwards DG, Rose WC, Fadel PJ, Farquhar WB. Exaggerated sympathetic and pressor responses to handgrip exercise in older hypertensive humans: role of the muscle metaboreflex. Am J Physiol Heart Circ Physiol 2010;299:H1318-27. [PMID: 20802135 DOI: 10.1152/ajpheart.00556.2010] [Citation(s) in RCA: 155] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]

Fu Q, Vangundy TB, Galbreath MM, Shibata S, Jain M, Hastings JL, Bhella PS, Levine BD. Cardiac origins of the postural orthostatic tachycardia syndrome. J Am Coll Cardiol 2010;55:2858-68. [PMID: 20579544 DOI: 10.1016/j.jacc.2010.02.043] [Citation(s) in RCA: 224] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2009] [Revised: 01/06/2010] [Accepted: 02/01/2010] [Indexed: 11/29/2022]

Abstract

OBJECTIVES

The purpose of this study was to test the hypothesis that a small heart coupled with reduced blood volume contributes to the postural orthostatic tachycardia syndrome (POTS) and that exercise training improves this syndrome.

BACKGROUND

Patients with POTS have marked increases in heart rate during orthostasis. However, the underlying mechanisms are unknown and the effective therapy is uncertain.

METHODS

Twenty-seven POTS patients underwent autonomic function tests, cardiac magnetic resonance imaging, and blood volume measurements. Twenty-five of them participated in a 3-month specially designed exercise training program with 19 completing the program; these patients were re-evaluated after training. Results were compared with those of 16 healthy controls.

RESULTS

Upright heart rate and total peripheral resistance were greater, whereas stroke volume and cardiac output were smaller in patients than in controls. Baroreflex function was similar between groups. Left ventricular mass (median [25th, 75th percentiles], 1.26 g/kg [1.12, 1.37 g/kg] vs. 1.45 g/kg [1.34, 1.57 g/kg]; p < 0.01) and blood volume (60 ml/kg [54, 64 ml/kg] vs. 71 ml/kg [65, 78 ml/kg]; p < 0.01) were smaller in patients than in controls. Exercise training increased left ventricular mass and blood volume by approximately 12% and approximately 7% and decreased upright heart rate by 9 beats/min [1, 17 beats/min]. Ten of 19 patients no longer met POTS criteria after training, whereas patient quality of life assessed by the 36-item Short-Form Health Survey was improved in all patients after training.

CONCLUSIONS

Autonomic function was intact in POTS patients. The marked tachycardia during orthostasis was attributable to a small heart coupled with reduced blood volume. Exercise training improved or even cured this syndrome in most patients. It seems reasonable to offer POTS a new name based on its underlying pathophysiology, the "Grinch syndrome," because in this famous children's book by Dr. Seuss, the main character had a heart that was "two sizes too small."

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Ram CVS. Could baroreceptor activation therapy be the future for treating hypertension and other chronic cardiovascular conditions? J Clin Hypertens (Greenwich) 2010;12:288-91. [PMID: 20433550 PMCID: PMC8673221 DOI: 10.1111/j.1751-7176.2009.00252.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2009] [Accepted: 11/14/2009] [Indexed: 11/30/2022]

Fisher JP, Fadel PJ. Therapeutic strategies for targeting excessive central sympathetic activation in human hypertension. Exp Physiol 2010;95:572-80. [PMID: 20304932 DOI: 10.1113/expphysiol.2009.047332] [Citation(s) in RCA: 70] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]

Pavithran P, Prakash ES, Dutta TK, Madanmohan T. Effect of antihypertensive drug therapy on short-term heart rate variability in newly diagnosed essential hypertension. Clin Exp Pharmacol Physiol 2010;37:e107-13. [DOI: 10.1111/j.1440-1681.2009.05295.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]

Rabbitts JA, Strom NA, Sawyer JR, Curry TB, Dietz NM, Roberts SK, Kingsley-Berg SM, Charkoudian N. Influence of endogenous angiotensin II on control of sympathetic nerve activity in human dehydration. J Physiol 2009;587:5441-9. [PMID: 19805740 DOI: 10.1113/jphysiol.2009.176693] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open

Charkoudian N, Rabbitts JA. Sympathetic neural mechanisms in human cardiovascular health and disease. Mayo Clin Proc 2009;84:822-30. [PMID: 19720780 PMCID: PMC2735432 DOI: 10.4065/84.9.822] [Citation(s) in RCA: 144] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]

Charkoudian N, Rabbitts JA. Sympathetic neural mechanisms in human cardiovascular health and disease. Mayo Clin Proc 2009;84:822-30. [PMID: 19720780 PMCID: PMC2735432 DOI: 10.1016/s0025-6196(11)60492-8] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]

Prakash ES, Fink GD. Could hypertension possibly be adaptive? Clin Exp Pharmacol Physiol 2009;37:e99-e106. [PMID: 19719749 DOI: 10.1111/j.1440-1681.2009.05284.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]

Fu Q, Levine BD. Autonomic circulatory control during pregnancy in humans. Semin Reprod Med 2009;27:330-7. [PMID: 19530067 DOI: 10.1055/s-0029-1225261] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]

Lohmeier TE, Hildebrandt DA, Dwyer TM, Iliescu R, Irwin ED, Cates AW, Rossing MA. Prolonged activation of the baroreflex decreases arterial pressure even during chronic adrenergic blockade. Hypertension 2009;53:833-8. [PMID: 19273736 PMCID: PMC2698596 DOI: 10.1161/hypertensionaha.109.128884] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]

Abstract

Previous studies suggest that prolonged electric activation of the baroreflex may reduce arterial pressure more than chronic blockade of alpha(1)- and beta(1,2)-adrenergic receptors. To determine whether central inhibition of sympathetic outflow has appreciable effects to chronically reduce arterial pressure by actions distinct from well-established mechanisms, we hypothesized that chronic baroreflex activation would lower arterial pressure substantially even during complete alpha(1)- and beta(1,2)-adrenergic receptor blockade. This hypothesis was tested in 6 dogs during adrenergic blockade (AB; 18 days) with and without electric activation of the carotid baroreflex (7 days). During chronic AB alone, there was a sustained decrease in the mean arterial pressure of 21+/-2 mm Hg (control: 95+/-4 mm Hg) and an approximately 3-fold increase in plasma norepinephrine concentration (control: 138+/-6 pg/mL), likely attributed to baroreceptor unloading. In comparison, during AB plus prolonged baroreflex activation, plasma norepinephrine concentration decreased to control levels, and mean arterial pressure fell an additional 10+/-1 mm Hg. Because of differences in plasma norepinephrine concentration, we also tested the acute blood pressure-lowering effects of MK-467, a peripherally acting alpha(2)-antagonist. After administration of MK-467, there was a significantly greater fall in arterial pressure during AB (15+/-3 mm Hg) than during AB plus prolonged baroreflex activation (7+/-3 mm Hg). These findings suggest that reflex-induced increases in sympathetic activity attenuate reductions in arterial pressure during chronic AB and that inhibition of central sympathetic outflow by prolonged baroreflex activation lowers arterial pressure further by previously undefined mechanisms, possibly by diminishing attendant activation of postjunctional alpha(2)-adrenergic receptors.

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Claassen JAHR, Levine BD, Zhang R. Cerebral vasomotor reactivity before and after blood pressure reduction in hypertensive patients. Am J Hypertens 2009;22:384-91. [PMID: 19229191 DOI: 10.1038/ajh.2009.2] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open

Central sympathetic overactivity: maladies and mechanisms. Auton Neurosci 2009;148:5-15. [PMID: 19268634 DOI: 10.1016/j.autneu.2009.02.003] [Citation(s) in RCA: 151] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2009] [Revised: 02/06/2009] [Accepted: 02/10/2009] [Indexed: 12/20/2022]

Fu Q, Okazaki K, Shibata S, Shook RP, VanGunday TB, Galbreath MM, Reelick MF, Levine BD. Menstrual cycle effects on sympathetic neural responses to upright tilt. J Physiol 2009;587:2019-31. [PMID: 19237424 DOI: 10.1113/jphysiol.2008.168468] [Citation(s) in RCA: 109] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open

Abstract

Young women are more susceptible to orthostatic intolerance than men, though the sex-specific pathophysiology remains unknown. As blood pressure (BP) is regulated through the baroreflex mechanism, we tested the hypothesis that baroreflex control of muscle sympathetic nerve activity (MSNA) during orthostasis is impaired in women and can be affected by the menstrual cycle. MSNA and haemodynamics were measured supine and during a graded upright tilt (30 deg for 6 min, 60 deg for 45 min or till presyncope) in 11 young men and 11 women during the early follicular (EFP) and mid-luteal phase (MLP) of the menstrual cycle. Sympathetic baroreflex sensitivity was quantified using the slope of the linear correlation between total activity and diastolic BP during spontaneous breathing. Baroreflex function was further assessed during a Valsalva manoeuvre (VM). Although MSNA burst frequency responses during tilting were similar between sexes and menstrual phases, increases in total activity were lower in women during EFP than MLP (P = 0.030), while total peripheral resistance and plasma noradrenaline were not similarly lower; upright total activity tended to be lower in women during EFP than men (P = 0.102). Sympathetic baroreflex sensitivity did not differ between sexes (P = 0.676) supine (-281 +/- 46 (S.E.M.) units beat(-1) mmHg(-1) in men vs -252 +/- 52 in EFP and -272 +/- 40 in MLP in women), at 30 deg tilt (-648 +/- 129 vs -611 +/- 79 and -487 +/- 94), and at 60 deg tilt (-792 +/- 135 vs -831 +/- 92 and -814 +/- 142); this sensitivity was not affected by the menstrual cycle (P = 0.747). Similar sympathetic baroreflex sensitivity between sexes and phases was also observed during the VM. Cardiovagal baroreflex sensitivity assessed during decreasing BP (i.e. early phase II of the VM) was comparable between sexes, but it was greater in men than women during increasing BP (i.e. phase IV); the menstrual cycle had no influences on cardiovagal baroreflex sensitivity. We conclude that the menstrual cycle affects sympathetic neural responses but not sympathetic baroreflex sensitivity during orthostasis, though upright vasomotor sympathetic activity is not clearly different between men and women. Not only sympathetic but also cardiovagal baroreflex sensitivity is similar between sexes and menstrual phases during a hypotensive stimulus. However, cardiovagal baroreflex-mediated bradycardia during a hypertensive stimulus is different between sexes but not affected by the menstrual cycle. Thus, other factors rather than sympathetic baroreflex control mechanisms contribute to sex differences in orthostatic tolerance in young humans.

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Sympathetic neural mechanisms in human hypertension. Curr Hypertens Rep 2009;10:241-7. [PMID: 18765097 DOI: 10.1007/s11906-008-0045-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Burns J, Mary DA, Mackintosh AF, Ball SG, Greenwood JP. The Effect of Chronic Anti-Hypertensive Therapy with Bendroflumethiazide on Sympathetic Drive. Clin Med Cardiol 2008. [DOI: 10.4137/117954682000200002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open

Fu Q, Vongpatanasin W, Levine BD. Neural and nonneural mechanisms for sex differences in elderly hypertension: can exercise training help? Hypertension 2008;52:787-94. [PMID: 18852385 DOI: 10.1161/hypertensionaha.108.118927] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]

Panoulas VF, Metsios GS, Pace AV, John H, Treharne GJ, Banks MJ, Kitas GD. Hypertension in rheumatoid arthritis. Rheumatology (Oxford) 2008;47:1286-98. [PMID: 18467370 DOI: 10.1093/rheumatology/ken159] [Citation(s) in RCA: 208] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open

Eguchi K, Pickering TG, Kario K. Why is blood pressure so hard to control in patients with type 2 diabetes? ACTA ACUST UNITED AC 2007;2:114-8. [PMID: 17684464 DOI: 10.1111/j.1559-4564.2007.06124.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]

Lohmeier TE, Dwyer TM, Irwin ED, Rossing MA, Kieval RS. Prolonged Activation of the Baroreflex Abolishes Obesity-Induced Hypertension. Hypertension 2007;49:1307-14. [PMID: 17438305 DOI: 10.1161/hypertensionaha.107.087874] [Citation(s) in RCA: 87] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]