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

• Published in: The Journal of physiology 2001-11, Vol.536 (3), p.977-983
• Main Authors: Dinenno, Frank A., Tanaka, Hirofumi, Stauffer, Brian L., Seals, Douglas R.
• Format: Article
• Language: English
• Subjects: 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; Research Papers; Vascular Resistance - physiology; Vasoconstriction - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.2001.00977.x

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 α‐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) α‐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, α‐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 α‐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 β‐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 α‐adrenergic vasoconstriction. This may have important physiological and pathophysiological implications for the ageing human.