Circulation, Vol 81, 491-497, Copyright © 1990 by American Heart Association
JA Vita, CB Treasure, EG Nabel, JM McLenachan, RD Fish, AC Yeung, VI Vekshtein, AP Selwyn and P Ganz
In animals, acetylcholine dilates normal arteries and produces
vasoconstriction in the presence of hypercholesterolemia, hypertension, or
atherosclerosis, reflecting endothelial cell dysfunction. In patients with
angiographically smooth coronary arteries, acetylcholine has been reported
to produce both vasodilation and constriction. To test the hypothesis that
the acetylcholine response relates to risk factors for coronary artery
disease, acetylcholine 10(-8) to 10(-6) M was infused into the left
anterior descending or circumflex coronary artery, and diameter changes
were assessed with quantitative angiography in 34 patients with
angiographically smooth coronary arteries. The acetylcholine response
ranged from +37% (dilation) to - 53% (constriction) at the peak
acetylcholine dose. All coronary arteries dilated in response to
nitroglycerin (26 +/- 17%), suggesting an abnormality of endothelial
function in the patients with a constrictor response to acetylcholine. By
multiple stepwise regression analysis, serum cholesterol (p less than
0.01), male gender (p less than 0.001), family history (p less than 0.05),
age (p less than 0.05), cholesterol level (p less than 0.01), and total
number of risk factors (p less than 0.0001) were independently associated
with the acetylcholine response. Thus, coronary risk factors are associated
with loss of endothelium-dependent vasodilation. The development of
vasoconstriction is likely to be an abnormality of endothelial function
that precedes atherosclerosis or an early marker of atherosclerosis not
detectable by angiography.
ARTICLES
Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
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