Circulation, Vol 85, 1390-1397, Copyright © 1992 by American Heart Association
JA Vita, CB Treasure, AC Yeung, VI Vekshtein, GM Fantasia, RD Fish, P Ganz and AP Selwyn
BACKGROUND. Studies in patients undergoing cardiac catheterization have
demonstrated that normal coronary arteries dilate and atherosclerotic
arteries constrict in response to exercise and the cold pressor test, but
the mechanisms are unknown. These vasomotor responses are mirrored by the
vasomotor response to the endothelium-dependent agent acetylcholine.
Exercise and the cold pressor test are associated with adrenergic
stimulation and increased circulating catecholamines. The present study
tested the hypothesis that coronary arteries with intact endothelial
function are relatively resistant to the constrictor effects of
catecholamines, whereas arteries with loss of endothelial function have
increased sensitivity to catecholamine-induced constriction. METHODS AND
RESULTS. The vasomotor function of the coronary endothelium was assessed by
serial acetylcholine infusions (final concentration, 10(-8) to 10(-6) M) in
30 segments in 15 patients with minimal or no evidence of coronary
atherosclerosis. The acetylcholine responses were related to the vasomotor
response to intracoronary phenylephrine infusion (final concentration,
10(-9) to 10(-6) M) in the same segments. In the group of 18 segments that
constricted to acetylcholine, there was a constrictor response to
phenylephrine at an approximately 100-fold lower concentration than the
group of 12 segments that did not constrict to acetylcholine. CONCLUSIONS.
These results suggest that the endothelial dysfunction that characterizes
early and late atherosclerosis is associated with a marked increase in
sensitivity to the constrictor effects of catecholamines. This finding may
explain the constrictor responses of atherosclerotic coronary arteries to
exercise and the cold pressor test. In stenotic coronary arteries this
mechanism may play a role in the production of myocardial ischemia.
ARTICLES
Patients with evidence of coronary endothelial dysfunction as assessed by acetylcholine infusion demonstrate marked increase in sensitivity to constrictor effects of catecholamines
Department of Medicine, Brigham and Women's Hospital-Brockton/West Roxbury Veterans Administration Medical Center, Boston, Mass. 02115.
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