Reductions in basal limb blood flow and vascular conductance with human ageing: role for augmented alpha-adrenergic vasoconstriction.

1. Basal whole-limb blood flow and vascular conductance decrease with age in men. We determined whether these age-associated changes in limb haemodynamics are mediated by tonically augmented sympathetic alpha-adrenergic vasoconstriction. 2. Seven young (28 +/- 2 years; mean +/- S.E.M.) and eight older (64 +/- 2 years) healthy, normotensive adult men were studied. Baseline femoral artery blood flow (Doppler ultrasound) and calculated vascular conductance were 29 and 31 % lower, respectively, and vascular resistance was 53 % higher in the older men (all P < 0.001). 3. Local (intra-femoral artery) alpha-adrenergic receptor blockade with phentolamine evoked greater increases in femoral blood flow (105 +/- 11 vs. 60 +/- 6 %) and vascular conductance (125 +/- 13 vs. 66 +/- 7 %), and reductions in vascular resistance (55 +/- 2 vs. 39 +/- 3 %) in the experimental limb of the older compared with the young men (all P < 0.001). As a result, alpha-adrenergic receptor blockade eliminated the significance of the age-associated differences in absolute levels of femoral blood flow (500 +/- 51 vs. 551 +/- 35 ml min(-1)), vascular conductance (6.02 +/- 0.73 vs. 6.33 +/- 0.26 U), and vascular resistance (0.17 +/- 0.03 vs. 0.16 +/- 0.01 U; P = 0.4-0.8, n.s.). Femoral haemodynamics in the control limb were unaffected by phentolamine administration in the contralateral (experimental) limb. Complete alpha-adrenergic receptor blockade was demonstrated by the absence of vasoconstriction in the experimental limb in response to the cold pressor test. Local propranolol was administered to control for any beta-adrenergic effects of phentolamine. Propranolol did not affect haemodynamics in the experimental or control limbs. 4. Our results indicate that the age-related reductions in basal limb blood flow and vascular conductance are mediated largely by chronically elevated sympathetic alpha-adrenergic vasoconstriction. This may have important physiological and pathophysiological implications for the ageing human.