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
ORIGINAL ABSTRACT from the AMERICAN HEART ASSOCIATION