CORONARY VASCULAR NITRIC-OXIDE ACTIVITY IN HYPERTENSION AND HYPERCHOLESTEROLEMIA - COMPARISON OF ACETYLCHOLINE AND SUBSTANCE-P

Background Whether the abnormal responses of the human coronary circul ation to acetylcholine in patients with hypertension and hypercholeste rolemia extend to other, nonmuscarinic stimulators of the endothelium and whether this signifies a specific abnormality of NO is not known. Methods and Results We studied 26 patients with angiographically norma l coronary arteries, 10 without risk factors, and 16 with either hyper tension (n=9) and/or hypercholesterolemia (n=10). Dose-response curves were performed with acetylcholine, substance P, and sodium nitropruss ide before and after N-G-monomethyl-L-arginine (L-NMMA). Substance P p roduced predominantly epicardial coronary dilation, whereas the dilati ng effect of acetylcholine was mainly microvascular. There was no corr elation between the responses to the two drugs. L-NMMA did not affect the response to sodium nitroprusside, but it suppressed dilation in re sponse to both substance P and acetylcholine, suggesting that the latt er promote bioavailability of NO from the coronary vascular endotheliu m. Compared with patients without risks, those with hypercholesterolem ia and hypertension had significantly reduced vasodilation with substa nce P:21% versus 12.6% (P=.004) increase in epicardial coronary diamet er and 35% versus 19% (P<.05) decrease in vascular resistance. Similar differences were noted with acetylcholine but not with sodium nitropr usside or adenosine. Epicardial and microvascular dilations with subst ance P or acetylcholine after L-NMMA were similar in patients with and without risk factors, indicating that the reduced effect of endotheli um-dependent vasodilators in those with hypertension and hypercholeste rolemia is due to diminished NO activity. Conclusions (1) Substance P- and acetylcholine-induced coronary vasodilation, like that to acetylc holine, is at least partly due to stimulation of NO activity, indicati ng that the dysfunction of the coronary vascular endothelial cell laye r is not restricted to muscarinic receptors. (2) Hypertension and hype rcholesterolemia are associated with depression of both basal and phar macologically stimulated bioavailability of NO.