Ageing and leg postjunctional alpha-adrenergic vasoconstrictor responsiveness in healthy men

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 alpha1-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 (alpha1-agonist) and dexmedetomidine (alpha2-agonist) were assessed. Consistent with previous data, resting femoral blood flow and FVC were approximately 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 alpha1- and alpha2-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.

Figure 1. Leg vasoconstrictor responses to tyramine in young and older men

Percentage changes in femoral blood flow (A) and vascular conductance (B) in response to all three doses of tyramine (evokes endogenous NA release) were significantly reduced in older compared with young men.

Figure 2. Leg vasoconstrictor responses to α₁-adrenoceptor stimulation in young and older men

Percentage changes in femoral blood flow (A) and vascular conductance (B) in response to all three doses of phenylephrine (direct α₁-adrenoceptor stimulation) were significantly reduced in older compared with young men.

Figure 3. Leg vasoconstrictor responses to α₂-adrenoceptor stimulation in young and older men

Percentage changes in femoral blood flow (A) and vascular conductance (B) in response to all three doses of dexmedetomidine (direct α₂-adrenoceptor stimulation) were significantly reduced in older compared with young men.

Figure 4. Femoral artery (conduit vessel) vasoconstriction in response to direct α₁- and α₂-adrenoceptor stimulation

Percentage changes in common femoral artery diameter were significantly reduced in response to all three doses of phenylephrine (α₁-agonist; A) and dexmedetomidine (α₂-agonist; B) in older compared with young men.