Ageing and leg postjunctional α‐adrenergic vasoconstrictor responsiveness in healthy men

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Abstract
Muscle sympathetic vasoconstrictor nerve activity increases with advancing age, but does not result in elevated forearm vasoconstrictor tone because of a selective reduction in α1‐adrenoceptor responsiveness. In contrast, the leg circulation of older adults is under greater tonic sympathetic vasoconstriction, but it is unclear whether α‐adrenoceptor responsiveness is altered with age. In the present study, we tested the hypothesis that postjunctional α‐adrenergic vasoconstrictor responsiveness is reduced in the leg circulation with age. We measured femoral blood flow (Doppler ultrasound) and calculated the femoral vascular conductance (FVC) responses to α‐adrenoceptor stimulation during local blockade of β‐adrenoceptors in 12 young (24 ± 1 year) and seven healthy older men (62 ± 2 year). Whole‐leg vasoconstrictor responses to local intrafemoral artery infusions of tyramine (evokes noradrenaline (NA) release), phenylephrine (α1‐agonist) and dexmedetomidine (α2‐agonist) were assessed. Consistent with previous data, resting femoral blood flow and FVC were ∼30% lower in older compared with young men (P < 0.05). Maximal vasoconstrictor responses to tyramine (−30 ± 3 versus−41 ± 3%), phenylephrine (−25 ± 4 versus−45 ± 5%), and dexmedetomidine (−22 ± 4 versus−44 ± 3%) were all significantly lower in older compared with young men (all P < 0.05). Our results indicate that human ageing is associated with a reduction in leg postjunctional α‐adrenoceptor responsiveness to endogenous NA release, and this reduction is evident for both α1‐ and α2‐adrenoceptors. However, given that basal leg vascular conductance is reduced with age and is primarily mediated by sympathetic vasoconstriction, impaired α‐adrenoceptor responsiveness does not negate the ability of the sympathetic nervous system to evoke greater tonic vasoconstriction in the leg vasculature of older men.
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