Role of α-adrenergic vasoconstriction in regulating skeletal muscle blood flow and vascular conductance during forearm exercise in ageing humans

Human ageing is associated with attenuated skeletal muscle blood flow during exercise. It is unknown whether elevated sympathetic nervous system activity with ageing limits skeletal muscle blood flow during exercise. Determining the role of the sympathetic nervous system in regulating blood flow in healthy ageing is clinically relevant as age-related changes in the sympathetic nervous system are exacerbated with many diseases associated with impaired tissue perfusion. In the present study, compared to young adults, older adults demonstrate impaired skeletal muscle blood flow during graded handgrip exercise, and this is due to reductions in vascular conductance. Second, the increase in muscle blood flow and vascular conductance during exercise after removal of sympathetic -adrenergic vasoconstrictor tone in older adults was lower compared to young adults, similar to what was observed under control conditions. As such, the age-associated impairment in exercising muscle blood flow and vascular conductance persisted during local adrenoreceptor blockade. AbstractIn healthy humans, ageing is typically associated with reduced skeletal muscle blood flow and vascular conductance during exercise. Further, there is a marked increase in resting sympathetic nervous system (SNS) activity with age, yet whether augmented SNS-mediated -adrenergic vasoconstriction contributes to the age-associated impairment in exercising muscle blood flow and vascular tone in humans is unknown. We tested the hypothesis that SNS-mediated vasoconstriction is greater in older than young adults and limits muscle (forearm) blood flow (FBF) during graded handgrip exercise (5, 15, 25% maximal voluntary contraction (MVC)). FBF was measured (Doppler ultrasound) and forearm vascular conductance (FVC) was calculated in 11 young (21 +/- 1years) and 12 older (62 +/- 2years) adults in control conditions and during combined local - and -adrenoreceptor blockade via intra-arterial infusions of phentolamine and propranolol, respectively. Under control conditions, older adults exhibited significantly lower FBF and FVC at 15% MVC exercise (22.6 +/- 1.3 vs. 29 +/- 3.3mlmin(-1) 100g forearm fat-free mass (FFM)(-1) and 21.7 +/- 1.2 vs. 33.6 +/- 4.0mlmin(-1) 100g FFM-1 100mmHg(-1); P<0.05) and 25% MVC exercise (37.4 +/- 1.4 vs. 46.0 +/- 4.9mlmin(-1) 100g FFM-1 and 33.7 +/- 1.4 vs. 49.0 +/- 5.7mlmin(-1) 100g FFM-1 100mmHg(-1); P<0.05), whereas there was no age group difference at 5% MVC exercise. Local adrenoreceptor blockade increased FBF and FVC at rest and during exercise in both groups, although the increase in FBF and FVC from rest to steady-state exercise was similar in young and older adults across exercise intensities, and thus the age-associated impairment in FBF and FVC persisted. Our data indicate that during graded intensity handgrip exercise, the reduced FVC and subsequently lower skeletal muscle blood flow in older healthy adults is not due to augmented sympathetic vasoconstriction, but rather due to impairments in local signalling or structural limitations in the peripheral vasculature with advancing age.