Journal
JOURNAL OF PHYSIOLOGY-LONDON
Volume 582, Issue 1, Pages 63-71Publisher
BLACKWELL PUBLISHING
DOI: 10.1113/jphysiol.2007.130591
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Funding
- NIA NIH HHS [R03 AG027150, AG027150, AG022337, K01 AG022337] Funding Source: Medline
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Muscle sympathetic vasoconstrictor nerve activity increases with advancing age, but does not result in elevated forearm vasoconstrictor tone because of a selective reduction in alpha(1)-adrenoceptor responsiveness. In contrast, the leg circulation of older adults is under greater tonic sympathetic vasoconstriction, but it is unclear whether alpha-adrenoceptor responsiveness is altered with age. In the present study, we tested the hypothesis that postjunctional alpha-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 alpha-adrenoceptor stimulation during local blockade of beta-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 (alpha(1)-agonist) and dexmedetomidine (alpha(2)-agonist) were assessed. Consistent with previous data, resting femoral blood flow and FVC were similar to 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 alpha-adrenoceptor responsiveness to endogenous NA release, and this reduction is evident for both alpha(1)- and alpha(2)-adrenoceptors. However, given that basal leg vascular conductance is reduced with age and is primarily mediated by sympathetic vasoconstriction, impaired alpha-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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