Sympathetic vasoconstriction in skeletal muscle: Modulatory effects of aging, exercise training, and sex

The sympathetic nervous system (SNS) is a critically important regulator of the cardiovascular system. The SNS controls cardiac output and its distribution, as well as peripheral vascular resistance and blood pressure at rest and during exercise. Aging is associated with increased blood pressure and decreased skeletal muscle blood flow at rest and in response to exercise. The mechanisms responsible for the blunted skeletal muscle blood flow response to dynamic exercise with aging have not been fully elucidated; however, increased muscle sympathetic nerve activity (MSNA), elevated vascular resistance and a decline in endothelium-dependent vasodilation are commonly reported in older adults. In contrast to aging, exercise training has been shown to reduce blood pressure and enhance skeletal muscle vascular function. Exercise training has been shown to enhance nitric oxide-dependent vascular function and may improve the vasodilatory capacity of the skeletal muscle vasculature; however, surprisingly little is known about the effect of exercise training on the neural control of circulation. The control of blood pressure and skeletal muscle blood flow also differs between males and females. Blood pressure and MSNA appear to be lower in young females compared to males. However, females experience a larger increase in MSNA with aging compared to males. The mechanism(s) for the altered SNS control of vascular function in females remain to be determined. Novelty: • This review will summarize our current understanding of the effects of aging, exercise training and sex on sympathetic vasoconstriction at rest and during exercise. • Areas where additional research is needed are also identified.

Comparison of Resveratrol Supplementation and Energy Restriction Effects on Sympathetic Nervous System Activity and Vascular Reactivity: A Randomized Clinical Trial

Background: Chronic sympathetic nervous system activation is associated with endothelial dysfunction and cardiometabolic disease, which may be modulated by resveratrol (RSV) and energy restriction (ER). This study aimed to examine the effects of RSV and ER on plasma noradrenaline (NA), flow-mediated vasodilation (ed-FMD), and endothelium-independent nitrate-mediated vasodilation (ei-NMD). Methods: The study included 48 healthy adults randomized to 30-days intervention of RSV or ER. Results: Waist circumference, total cholesterol, HDL-c, LDL-c, apoA-I, and plasma NA decreased in the ER group, whilst RSV increased apoB and total cholesterol, without changing plasma NA. No effects on vascular reactivity were observed in both groups. Plasma NA change was positively correlated with total cholesterol (r = 0.443; p = 0.002), triglycerides (r = 0.438; p = 0.002), apoA-I (r = 0.467; p = 0.001), apoB (r = 0.318; p = 0.032) changes, and ei-NMD (OR = 1.294; 95%CI: 1.021–1.640). Conclusions: RSV does not improve cardiometabolic risk factors, sympathetic activity, and endothelial function. ER decreases plasma NA and waist circumference as well as improves blood lipids, but does not modify endothelial function. Finally, plasma NA was associated with ei-NMD, which could be attributed to a higher response to nitrate in patients with greater resting sympathetic vasoconstriction.

The Cardiovascular Conundrum in Ethnic and Sexual Minorities: A Potential Biomarker of Constant Coping With Discrimination

Background: A paradoxical profile of greater elevated sympathetic vasoconstriction (increased total peripheral resistance, TPR) and increased vagally-mediated heart rate variability (HRV) -the so-called Cardiovascular Conundrum- has been reported in African Americans (AAs) both at rest and in response to orthostasis. Whereas some authors have attributed this pattern to genetic factors, others have pointed to the potential role of coping with repeated racial discrimination.Objective: To disentangle between these alternative explanations, we have examined the hemodynamic profile of another population that is likely to be exposed to episodes of discrimination, i.e., sexual minorities.Methods: The first study was conducted on a sample of AAs and European Americans (EAs) with the aim of replicating previous results on the Cardiovascular Conundrum. In the second study, lesbian, gay, and bisexual (LGB) people, matched by age and sex with heterosexual participants, underwent a hemodynamic and autonomic assessment at rest and during an emotional (in the experimental group, both LGB-related and non LGB related), and a cognitive stressor.Results: The first study confirmed a pattern of higher resting HRV, paired with higher TPR, in AAs compared to EAs. In the second study, compared to heterosexuals, the LGB group showed the Cardiovascular Conundrum pattern, characterized by greater HRV and higher TPR at baseline and a more vascular hemodynamic profile and prominent compensation deficit in response to both tasks, and particularly during the LGB-related emotional task. However, in LGB only, the vascular response was negatively correlated with perceived discrimination.Conclusion: Present preliminary results are discussed in terms of maladaptive physiological consequences of exposure to chronic stress and the chronic use of dysfunctional emotion regulation strategies such as suppression.

Hyperinsulinemia blunts sympathetic vasoconstriction: A possible role of β-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.

Effects of sex and exercise training on β-adrenoreceptor mediated opposition of evoked sympathetic vasoconstriction in resting and contracting muscle of rats

This study investigated the hypothesis that β-adrenoreceptor mediated inhibition of sympathetic vasoconstriction would be enhanced in female compared to male rats, and that exercise training would augment β-adrenoreceptor inhibition of sympathetic vasoconstriction in male and female rats. Sprague-Dawley rats were randomized into sedentary (Male: n=7; Female: n=8) and exercise trained (Male: n=9; Female: n=9) groups. Following 4 weeks of exercise training or sedentary behavior, rats were anesthetized and surgically instrumented for stimulation of the lumbar sympathetic chain, muscle contraction and measurement of arterial blood pressure and femoral artery blood flow (FBF). Femoral vascular conductance (FVC) was calculated as FBF/mean arterial pressure. The percentage change of FVC in response to sympathetic stimulation delivered at 2 and 5 Hz was measured at rest and during contraction of the triceps surae muscles before and after β-adrenoreceptor blockade (Propranolol;0.075 mg·kg-1, IV). We found that, at rest, β-adrenoreceptor blockade decreased (main effect of drug, 2Hz: P <0.001; 5Hz: P<0.001) sympathetic vasoconstriction. During contraction, sympathetic vasoconstrictor responsiveness was lower (main effect of sex, 2Hz: P=0.001; 5Hz: P=0.023) in female compared to male rats, and sympatholysis was enhanced (main effect of sex, 2 Hz: P=0.001; 5Hz: P<0.001) in female rats. β-adrenoreceptor blockade decreased (main effect of drug, 2Hz: P=0.049; 5Hz: P<0.001) evoked sympathetic vasoconstriction in contracting muscle. The present study demonstrated that β-adrenoreceptors do not blunt sympathetic vasoconstriction in resting or contracting skeletal muscle of male or female rats. Sympatholysis was enhanced in female rats, however, this was not attributable to β-adrenoreceptor mediated blunting of sympathetic vasoconstriction.

Functional sympatholysis is preserved in healthy young Black men during rhythmic handgrip exercise

Black men have attenuated increases in forearm vascular conductance (FVC) and forearm blood flow (FBF) during moderate- and high-intensity rhythmic handgrip exercise compared with White men, but the underlying mechanisms are unclear. Here, we tested for the first time the hypothesis that functional sympatholysis (i.e., attenuation of sympathetic vasoconstriction in the exercising muscles) is impaired in Black men compared with White men. Thirteen White and 14 Black healthy young men were studied. FBF (duplex Doppler ultrasound) and mean arterial pressure (MAP; Finometer) were measured at rest and during rhythmic handgrip exercise at 30% maximal voluntary contraction. FVC was calculated as FBF/MAP. Sympathetic activation was induced via lower body negative pressure (LBNP) at −20 Torr for 2 min at rest and from the 3rd to the 5th min of handgrip. Sympathetic vasoconstriction was assessed as percent reductions in FVC during LBNP. The groups presented similar resting FVC, FBF, and MAP. During LBNP at rest, reductions in FVC were not different between White (−35 ± 10%) and Black men (−32 ± 14%, P = 0.616), indicating similar reflex-induced sympathetic vasoconstriction. During handgrip exercise, there were minimal reductions in FVC with LBNP in either group (White: −1 ± 7%; Black: +1 ± 8%; P = 0.523), indicating functional sympatholysis in both groups. Thus, contrary to our hypothesis, our findings indicate a preserved functional sympatholysis in healthy young Black men compared with White men, suggesting that this mechanism does not appear to contribute to reduced exercise hyperemia during moderate-intensity rhythmic handgrip in this population.

Mechanisms of sympathetic restraint in human skeletal muscle during exercise: role of α-adrenergic and nonadrenergic mechanisms

Sympathetic restraint of vascular conductance to inactive skeletal muscle is critical to maintain blood pressure during moderate- to high-intensity whole body exercise. This investigation shows that cycle exercise-induced restraint of inactive skeletal muscle vascular conductance occurs primarily because of activation of α-adrenergic receptors. Furthermore, exercise-induced vasoconstriction restrains the subsequent vasodilatory response to hand-grip exercise; however, the restraint of active skeletal muscle vasodilation was in part due to nonadrenergic mechanisms. We conclude that α-adrenergic receptors are the primary but not exclusive mechanism by which sympathetic vasoconstriction restrains blood flow in humans during whole body exercise and that metabolic activity modulates the contribution of α-adrenergic receptors.

Vibrações, Ruído e Hipoacusia: associação fisiopatológica ou não?

Introduction / framework / objectives Vibrations and noise are two reasonably prevalent occupational risk factors and, in many situations, present together. If a pathophysiological association between them is real, it will be very relevant to verify this, in order to readjust, if necessary, the vibration and noise limits considered safe. Methodology This is an Scoping Review, initiated by a September 2019 survey of the “Cochrane Central Register of Controlled Trials databases, CINALH plus with full text, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, Cochrane Methodology Register, Nursing and Allied Health Collection: Comprehensive, MedicLatina, Academic Search Ultimate, Science Direct, SCOPUS and RCAAP.” Content Some researchers have quantified higher hearing losses in workers simultaneously exposed to noise and vibrations; however, workers exposed to vibration from work instruments are generally also exposed to higher levels of noise. If there is a pathophysiological link between these two occupational risk factors, it is believed that this may be related to the theory of sympathetic vasoconstriction (observed in white-finger syndrome) and may also damage the cochlea, producing ischemic damage to the hair cells. Another hypothesis points out that some work tools may give rise to vibrations that can reach the inner ear directly, through bone conduction (especially at the temporal level). Conclusions Most of the studies consulted did not have a very robust methodology that allows a rigorous evaluation of whether the most intense hypoacusis in individuals simultaneously exposed to vibration results from a true pathophysiological association, or if it is only a statistical bias. It would be interesting for occupational health teams to investigate on clients with workers simultaneously exposed to these two risk factors (and, if possible, with combinations of different intensities), in order to produce knowledge capable of enhancing occupational health and safety.

β-Adrenoreceptors do not oppose sympathetic vasoconstriction in resting and contracting skeletal muscle of male rats

Sympathetic nervous system (SNS) vasoconstriction is primarily achieved through the binding of norepinephrine (NE) to α-adrenoreceptors. However, NE may also bind to β-adrenoreceptors and cause vasodilation that may oppose/blunt SNS-mediated vasoconstriction. Therefore, this study investigated the hypothesis that β-adrenoreceptor–mediated vasodilation opposes evoked vasoconstriction in resting and contracting skeletal muscle. Male (n = 9) Sprague–Dawley rats were anesthetized and surgically instrumented for stimulation of the lumbar sympathetic chain and measurement of arterial blood pressure and femoral artery blood flow. The percentage change of femoral vascular conductance in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae skeletal muscle contraction before (control) and after β-adrenoreceptor blockade (propranolol; 0.075 mg·kg−1, intravenously). β-Adrenoreceptor blockade did not alter (P > 0.05) baseline hemodynamics or the hyperemic response to exercise. At the 2 Hz stimulation frequency, sympathetic vasoconstriction was similar (P > 0.05) in control and β-blockade conditions in resting (control, −34% ± 6%; β-blockade, −33% ± 8%) and contracting (control, −16% ± 6%; β-blockade, −14% ± 7%) muscle. At the 5 Hz stimulation frequency, sympathetic vasoconstrictor responsiveness was reduced (main effect of drug, P < 0.05) following β-blockade (rest: control, −52% ± 7%; β-blockade, −51% ± 9%; contraction: control, −32% ± 11%; β-blockade, −29% ± 13%). Novelty These data indicate that β-adrenoreceptor blockade did not augment sympathetic vasoconstriction at rest or during exercise. The study demonstrates that β-adrenoreceptors do not oppose evoked sympathetic vasoconstriction in resting or contracting skeletal muscle or contribute to functional sympatholysis.

Effect of acute dietary nitrate supplementation on sympathetic vasoconstriction at rest and during exercise

Dietary nitrate ([Formula: see text]) supplementation has been shown to reduce resting blood pressure. However, the mechanism responsible for the reduction in blood pressure has not been identified. Dietary [Formula: see text] supplementation may increase nitric oxide (NO) bioavailability, and NO has been shown to inhibit sympathetic vasoconstriction in resting and contracting skeletal muscle. Therefore, the purpose of this study was to investigate the hypothesis that acute dietary [Formula: see text] supplementation would attenuate sympathetic vasoconstrictor responsiveness at rest and during exercise. In a double-blind randomized crossover design, 12 men (23 ± 5 yr) performed a cold-pressor test (CPT) at rest and during moderate- and heavy-intensity alternate-leg knee-extension exercise after consumption of [Formula: see text] rich beetroot juice (~12.9 mmol [Formula: see text]) or a [Formula: see text]-depleted placebo (~0.13 mmol [Formula: see text]). Venous blood was sampled before and 2.5 h after the consumption of beetroot juice for the measurement of total plasma nitrite/[Formula: see text] [NOx]. Beat-by-beat blood pressure was measured by Finometer. Leg blood flow was measured at the femoral artery via Doppler ultrasound, and leg vascular conductance (LVC) was calculated. Sympathetic vasoconstrictor responsiveness was calculated as the percentage decrease in LVC in response to the CPT. Total plasma [NOx] was greater ( P < 0.001) in the [Formula: see text] (285 ± 120 µM) compared with the placebo (65 ± 30 µM) condition. However, mean arterial blood pressure and plasma catecholamines were not different ( P > 0.05) between [Formula: see text] and placebo conditions at rest or during moderate- and heavy-intensity exercise. Sympathetic vasoconstrictor responsiveness (Δ% LVC) was not different ( P > 0.05) between [Formula: see text] and placebo conditions at rest ([Formula: see text]: −33 ± 10%; placebo: −35 ± 11%) or during moderate ([Formula: see text]: −18 ± 8%; placebo: −20 ± 10%)- and heavy ([Formula: see text]: −12 ± 8%; placebo: −11 ± 9%)-intensity exercise. These data demonstrate that acute dietary [Formula: see text] supplementation does not alter sympathetic vasoconstrictor responsiveness at rest or during exercise in young healthy males. NEW & NOTEWORTHY Dietary nitrate may increase nitric oxide bioavailability, and nitric oxide has been shown to attenuate sympathetic vasoconstriction in resting and contracting skeletal muscle and enhance functional sympatholysis. However, the effect of dietary nitrate on sympathetic vasoconstrictor responsiveness is unknown. Acute dietary nitrate supplementation did not alter blood pressure or sympathetic vasoconstrictor responsiveness at rest or during exercise in young healthy males.