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

J Physiol. 2001 Nov 1;536(Pt 3):977-83. doi: 10.1111/j.1469-7793.2001.00977.x.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Adult
  • Aged
  • Aging / physiology*
  • Blood Pressure / physiology
  • Body Composition / physiology
  • Catheterization
  • Cold Temperature
  • Extremities / blood supply*
  • Femur / blood supply
  • Heart Rate / physiology
  • Humans
  • Infusions, Intra-Arterial
  • Leg / anatomy & histology
  • Male
  • Middle Aged
  • Phentolamine / pharmacology
  • Pressure
  • Propranolol / pharmacology
  • Receptors, Adrenergic, alpha / physiology*
  • Regional Blood Flow / physiology
  • Vascular Resistance / physiology*
  • Vasoconstriction / physiology*

Substances

  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • Receptors, Adrenergic, alpha
  • Propranolol
  • Phentolamine