The effects of angiotensin-converting enzyme inhibition on endothelial dysfunction: potential role in myocardial ischemia

Abstract

As is well known, the pathogenesis of coronary artery disease (CAD) and its clinical consequences, myocardial ischemia and infarction, are related both to atherosclerotic stenoses that limit increases in oxygen supply on demand and to inappropriate dilation or abnormal constriction of coronary arteries or microcirculation.1–3 One mechanism involved in disturbances of coronary vasomotion is endothelial dysfunction. The endothelium performs a number of regulatory activities that maintain vascular structure and function, including vascular tone, growth, hemostasis, inflammation, and redox state.2,4,5 In the physiologic state, vascular angiotensin-converting enzyme (ACE) helps maintain vessel tone. In endothelial dysfunction, however, the vascular ACE system is central to the pathogenesis of cardiovascular disease. ACE modulates the formation of angiotensin II, a potent vasoconstrictor whose effect is to decrease myocardial oxygen supply.6 ACE also promotes the degradation of bradykinin, a peptide that promotes the release of nitric oxide (NO). Nitric oxide is a potent vasodilator that has been shown in experimental studies to decrease tissue oxygen consumption.4,5,7 Such findings, coupled with the anti-ischemic effects of ACE inhibitors observed in patients with left ventricular dysfunction or acute myocardial infarction,8,9 suggest that ACE inhibition may have anti-ischemic effects in patients with myocardial ischemia and preserved ventricular function. A large ongoing study is evaluating the effects of an ACE inhibitor on ischemia-related events in patients with preserved ventricular function—the QUinapril Anti-ischemia and Symptoms of Angina Reduction (QUASAR) study.