Potential mechanisms for the effect of angiotensin-converting enzyme inhibitors on endothelial dysfunction: the role of nitric oxide

Abstract

Endothelium-dependent vasomotor responses in coronary arteries are impaired in patients with coronary artery disease and in those with risk factors for cardiovascular disease and angiographically normal coronary arteries. The impaired vasodilative response in these vessels is due largely to decreased bioactivity of the potent vasodilator, nitric oxide (NO). 1 Quyyumi A.A. Dakak N. Andrews N.P. Husain S. Arora S. Gilligan D.M. Panza J.A. Cannon III, R.O. Nitric oxide activity in the human coronary circulation impact of risk factors for coronary atherosclerosis. J Clin Invest. 1995; 95: 1747-1755 Crossref PubMed Scopus (404) Google Scholar In early studies 1 Quyyumi A.A. Dakak N. Andrews N.P. Husain S. Arora S. Gilligan D.M. Panza J.A. Cannon III, R.O. Nitric oxide activity in the human coronary circulation impact of risk factors for coronary atherosclerosis. J Clin Invest. 1995; 95: 1747-1755 Crossref PubMed Scopus (404) Google Scholar in subjects with angiographically normal coronary arteries with and without risk factors for coronary artery disease, we found that intracoronary administration of l-N-monomethyl arginine (l-NMMA), a specific inhibitor of the synthesis of NO from l-arginine via activity of NO synthase, resulted in increased resting vascular resistance, decreased epicardial diameter, and a decreased response to the endothelium-mediated vasodilative effects of acetylcholine in epicardial arteries and the coronary microvasculature. These effects were reversed by intracoronary administration of the NO precursor l-arginine (Figure 1 ). The vasoconstrictive effect of l-NMMA and the vasodilative effect of acetylcholine, as well as the inhibition of the effects of acetylcholine by l-NMMA, were greater in both epicardial arteries and the microvasculature of subjects without risk factors compared with those with risk factors. These findings suggested that NO contributes importantly to resting epicardial and coronary microvascular tone, that vasodilation in response to acetylcholine results primarily from increased production or activity of NO, and that coronary risk factors are associated with decreased resting and stimulated bioavailability of NO in the coronary circulation.