HDCN Article Review/Hyperlink

Gerhard M, Roddy M-A, Creager SJ, Creager MA

Aging progressively impairs endothelium-dependent vasodilation in forearm resistance vessels of humans

Hypertension (Apr) 27:849-853 1996

This study assessed methacholine-stimulated (endothelium-dependent) vasodilation of forearm resistance vessels as a function of age in 119 healthy subjects (19-69 years). Subjects were without evidence of hypercholesterolemia, diabetes, hypertension, history of cardiovascular disease or smoking, and were not taking any potentially vasoactive medications. Forearm vascular resistance was assessed by determining forearm blood flow (venous occlusion plethysmography) and blood pressure (indwelling brachial artery catheter) both in the basal state and following unilateral brachial infusion of endothelium-dependent (methacholine) and endothelium-independent (nitroprusside) vasodilators (both at doses of 0.03-10 ug/min). Systemic effects were excluded by the absence of an effect of blood pressure or on flow in the contralateral arm. The slope of each dose-blood flow response curve was taken as a measure of vasodilator responsivity; an approach novel to this study.

There was no change in nitropruside responsivity as a function of age but there was a highly significant regression of methacholine responsivity vs age (r=.81, p < 0.001); the slope decreased monotonically from 2.25 (20-29 yo) to 0.34 < 60-69 yo). In this healthy population there were significant univariate associations of methacholine responsivity with LDL and total cholesterol, but not with weight, blood pressure, or other lipid measures. In a stepwise multivariate regression only age was a significant predictor of methacholine responsivity.

Endothelium dependent relaxation is impaired in diabetes, atherosclerotic disease, and in the setting of some forms of experimental hypertension. A variety of smaller studies had previously demonstrated age-associated decreases of endothelium-dependent relaxation in conduit vessels from humans and in both conduit and some (but not all) resistance vessel preparations from laboratory animals. Since NO is an important endothelium-derived vasodilator and it exerts a variety of vasculoprotective effects, authors speculate that this age-associated endothelial dysfunction, due perhaps to cumulative oxidant stress, may predispose to atherosclerosis.

Comment: While this effect of age on the slope of the methacholine vasodilator dose response curve is striking and surely serves as a marker of some sort of endothelial dysfunction, its mechanism, relationship with NO synthesis, clinical significance, and possible pathogenetic consequences remain entirely speculative. Jason G. Umans, M.D., University of Chicago