The Arg16/Gly β2-adrenergic receptor polymorphism is associated with altered cardiovascular responses to isometric exercise

A polymorphism in the gene encoding the β2-adrenergic receptor (arginine or glycine at amino acid position 16) is associated with altered vasodilator responses to β2-agonists, which may modulate the pressor response to endogenous catecholamines during stress. To test the hypothesis that the Arg16/Gly polymorphism is associated with differences in acute pressor responses to sympathoexcitation, we measured mean arterial pressure (MAP, Finapres) and heart rate (HR, ECG) during mental stress (MS), cold pressor test (CPT), and handgrip (HG) to fatigue in 31 healthy, nonobese, normotensive adults (mean age ± SE: 31 ± 1; 16 females). Subjects were homozygous for Gly16 ( n = 16) or Arg16 ( n = 15). Both groups had similar baseline MAP (Arg16, 86 ± 3 mmHg; Gly16, 89 ± 2 mmHg; P = 0.4) and HR (Arg16, 68 ± 2 beats/min; Gly16, 65 ± 3 beats/min; P = 0.3). For MS and CPT, MAP and HR did not differ between genotype groups. Handgrip also produced similar increases in MAP; however, the change in HR was greater in the Gly16 homozygotes ( PANOVA = 0.001, genotype-by-time interaction). During HG, peak HR at fatigue was 100 ± 4 beats/min for Gly16 (54% increase from rest) vs. 93 ± 3 beats/min for Arg16 (37% increase). We conclude that the cardiovascular responses to MS and CPT do not differ between Gly16 and Arg16 homozygotes. However, the greater HR response to exercise in the Gly16 homozygotes may serve to maintain the pressor response (increased cardiac output) in the face of augmented peripheral vasodilation (decreased total peripheral resistance) in this group.

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Blunted cardiovascular responses to exercise in Parkinson’s disease patients: role of the muscle metaboreflex

Journal of Neurophysiology ◽

10.1152/jn.00308.2018 ◽

2018 ◽

Vol 120 (4) ◽

pp. 1516-1524 ◽

Cited By ~ 9

Author(s):

Jeann L. Sabino-Carvalho ◽

André L. Teixeira ◽

Milena Samora ◽

Maurício Daher ◽

Lauro C. Vianna

Keyword(s):

Blood Pressure ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cold Pressor Test ◽

Peripheral Resistance ◽

Cold Pressor ◽

Cardiovascular Responses ◽

Group Differences ◽

Muscle Metaboreflex ◽

Pressor Test

Patients with Parkinson’s disease (PD) exhibit attenuated cardiovascular responses to exercise. The underlying mechanisms that are potentially contributing to these impairments are not fully understood. Therefore, we sought to test the hypothesis that patients with PD exhibit blunted cardiovascular responses to isolated muscle metaboreflex activation following exercise. For this, mean blood pressure, cardiac output, and total peripheral resistance were measured using finger photoplethysmography and the Modelflow method in 11 patients with PD [66 ± 2 yr; Hoehn and Yahr score: 2 ± 1 a.u.; time since diagnosis: 7 ± 1 yr; means ± SD) and 9 age-matched controls (66 ± 3 yr). Measurements were obtained at rest, during isometric handgrip exercise performed at 40% maximal voluntary contraction, and during postexercise ischemia. Also, a cold pressor test was assessed to confirm that blunted cardiovascular responses were specific to exercise and not representative of generalized sympathetic responsiveness. Changes in mean blood pressure were attenuated in patients with PD during handgrip (PD: ∆25 ± 2 mmHg vs. controls: ∆31 ± 3 mmHg; P < 0.05), and these group differences remained during postexercise ischemia (∆17 ± 1 mmHg vs. ∆26 ± 1 mmHg, respectively; P < 0.01). Additionally, changes in total peripheral resistance were attenuated during exercise and postexercise ischemia, indicating blunted reflex vasoconstriction in patients with PD. Responses to cold pressor test did not differ between groups, suggesting no group differences in generalized sympathetic responsiveness. Our results support the concept that attenuated cardiovascular responses to exercise observed in patients with PD are, at least in part, explained by an altered skeletal muscle metaboreflex. NEW & NOTEWORTHY Patients with Parkinson’s disease (PD) presented blunted cardiovascular responses to exercise. We showed that cardiovascular response evoked by the metabolic component of the exercise pressor reflex is blunted in patients with PD. Furthermore, patients with PD presented similar pressor response during the cold pressor test compared with age-matched controls. Altogether, our results support the hypothesis that attenuated cardiovascular responses to exercise observed in patients with PD are mediate by an altered skeletal muscle metaboreflex.

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Hyperinsulinemia blunts sympathetic vasoconstriction: A possible role of β-adrenergic activation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00018.2021 ◽

2021 ◽

Author(s):

Jaqueline K. Limberg ◽

Rogerio Nogueira Soares ◽

Gavin Power ◽

Jennifer L. Harper ◽

James A. Smith ◽

...

Keyword(s):

Adrenergic Receptor ◽

Cold Pressor Test ◽

Peripheral Resistance ◽

Cold Pressor ◽

Insulin Stimulation ◽

Sympathetic Vasoconstriction ◽

Sympathetic Nervous ◽

Isolated Arteries ◽

Adrenergic Activation

Herein we report in a sample of healthy young men (n=14) and women (n=12) that hyperinsulinemia induces time-dependent decreases in total peripheral resistance and its contribution to the maintenance of blood pressure. In the same participants, we observe profound vasodilatory effects of insulin in the lower limb despite concomitant activation of the sympathetic nervous system. We hypothesized this prominent peripheral vasodilation is possibly due to an ability of the leg vasculature to escape sympathetic vasoconstriction during systemic insulin stimulation. Consistent with this notion, we demonstrate in a subset of healthy men (n=9) and women (n=7) that systemic infusion of insulin blunts sympathetically-mediated leg vasoconstriction evoked by a cold pressor test, a well-established sympathoexcitatory stimulus. Further substantiating this observation, we show in mouse aortic rings that insulin exposure suppresses epinephrine and norepinephrine-induced vasoconstriction. Notably, we found that such insulin-suppressing effects on catecholamine-induced constriction are diminished following β-adrenergic receptor blockade. In accordance, we also reveal that insulin augments β-adrenergic-mediated vasodilation in isolated arteries. Collectively, these findings support the idea that sympathetic vasoconstriction can be attenuated during systemic hyperinsulinemia in the leg vasculature of both men and women and that this phenomenon may be in part mediated by potentiation of β-adrenergic vasodilation neutralizing α-adrenergic vasoconstriction.

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Endothelin Receptor Blockade Blunts the Pressor Response to Acute Stress in Obese Men and Women

Journal of Applied Physiology ◽

10.1152/japplphysiol.00156.2021 ◽

2021 ◽

Author(s):

Cassandra C. Derella ◽

Anson M. Blanks ◽

Xiaoling Wang ◽

Matthew A. Tucker ◽

Chase Horsager ◽

...

Keyword(s):

Acute Stress ◽

Pressor Response ◽

Cold Pressor Test ◽

Cold Pressor ◽

Normal Weight ◽

Endothelin Receptor ◽

Treatment Results ◽

Endothelin 1 ◽

Endothelin System ◽

The Impact

Obesity is associated with dysregulation of the endothelin system. In obese individuals, an exaggerated pressor response to acute stress is accompanied by increased circulating endothelin-1. The impact of combined endothelin A/B receptor (ETA/B) antagonism on the stress-induced pressor response in overweight/obese individuals is unknown. Objective: To test the hypothesis that treatment with an ETA/B antagonist (bosentan) would reduce the stress-induced pressor response and arterial stiffness in overweight/obese compared to normal weight individuals. Methods: 40 participants [Normal weight (NW): n=20, BMI: 21.7 ± 2.4 kg/m2 & Overweight/obese (OB): n=20, BMI: 33.8 ± 8.2 kg/m2] were randomized to placebo or 125 mg of bosentan twice a day (250 mg total) for 3 days. Hemodynamics were assessed before, during, and after a cold pressor test (CPT). Endothelin-1 was assessed at baseline and immediately after CPT. Following a washout period, the same protocol was repeated with the opposite treatment. Results: The change from baseline in mean arterial pressure (MAP) during CPT following bosentan was significantly lower (p=0.039) in the OB group, compared to the NW group (OB: 28±12 vs LN: 34±15 mm Hg). Conclusions: These results suggest that ETA/B antagonism favorably blunts the pressor response to acute stress in overweight/obese individuals.

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Distribution of cardiac output during induced isometric exercise in dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1979.236.2.h218 ◽

1979 ◽

Vol 236 (2) ◽

pp. H218-H224 ◽

Cited By ~ 10

Author(s):

S. C. Crayton ◽

R. Aung-Din ◽

D. E. Fixler ◽

J. H. Mitchell

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Adrenergic Receptor ◽

Isometric Exercise ◽

Peripheral Resistance ◽

Minute Volume ◽

Adrenergic Blockade ◽

Limb Muscles ◽

Anesthetized Dogs ◽

Distribution Of Cardiac Output

Studies were designed to characterize the distribution of cardiac output during induced isometric exercise in anesthetized dogs. The response to isometric exercise involved significant increases in heart rate (+12 +/- 3%(SE)), mean arterial pressure (+13 +/- 2%), cardiac output (+26 +/- 8%), and respiratory minute volume (+75 +/- 26%); total peripheral resistance did not change significantly. Significant changes in blood flow were observed during isometric exercise in kidneys (-18 +/- 6%) and contracting limb muscles (+453 +/- 154%). Flow to liver (hepatic artery), spleen, brain, and myocardium remained near control values. Section of spinal dorsal roots L6-L7 abolished the responses to isometric exercise except for the increase in flow to exercising limb muscles. Alpha-adrenergic receptor blockade abolished the decrease in renal blood flow during isometric exercise; however, the increase in flow to exercising limb muscles was not affected by either alpha- or beta-adrenergic blockade.

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Abnormal sympathetic neural recruitment patterns and hemodynamic responses to cold pressor test in women with posttraumatic stress disorder

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00684.2019 ◽

2020 ◽

Vol 318 (5) ◽

pp. H1198-H1207 ◽

Cited By ~ 2

Author(s):

Jeung-Ki Yoo ◽

Mark B. Badrov ◽

Mu Huang ◽

Ryan A. Bain ◽

Raymond P. Dorn ◽

...

Keyword(s):

Posttraumatic Stress Disorder ◽

Posttraumatic Stress ◽

Stress Disorder ◽

Pressor Response ◽

Muscle Sympathetic Nerve Activity ◽

Cold Pressor Test ◽

Cold Pressor ◽

Pressor Test ◽

Activity Burst ◽

Circulatory Control

The novel findings of the present study are that women with posttraumatic stress disorder (PTSD) have an augmented pressor response to the sympathoexcitatory stimulus of a cold pressor test (CPT) compared with healthy control subjects. Although integrated muscle sympathetic nerve activity burst responses were not significantly different between groups, total sympathetic action potential discharge in response to the CPT was markedly elevated in women with PTSD exhibiting increased firing of low-threshold axons as well as the recruitment of latent subpopulations of larger-sized axons that are otherwise silent at baseline. Aberrant autonomic circulatory control in response to sympathoexcitatory stimulus may in part explain the propensity toward developing hypertension and cardiovascular disease in this population.

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