Amelioration by quinapril of myocardial infarction induced by coronary occlusion/reperfusion in a rabbit - Model of atherosclerosis - Possible mechanisms

Background-The increased severity of the myocardial injury produced by coro nary occlusion-reperfusion in models of atherosclerosis is associated with an increase in leukocyte accumulation in the ischemic myocardium. Expressio n of P-selectin, an adhesion molecule involved in the interaction between l eukocytes and endothelium, is increased in atherosclerotic vessels. Long-te rm angiotensin-converting enzyme (ACE) inhibition has been shown to reduce atherosclerotic vascular change in experimental models. Methods and Results-We examined changes in the size of the infarct resultin g from coronary occlusion/reperfusion in normally fed and cholesterol-fed r abbits that were chronically treated with quinapril. Infarct size was signi ficantly larger in the cholesterol-fed versus normally fed rabbits. ACE act ivity in the ischemic and nonischemic myocardium was significantly reduced by quinapril. Chronic quinapril administration significantly ameliorated th e increased myocardial injury in cholesterol-fed rabbits. Quinapril adminis tration markedly increased the myocardial cGMP content and reduced the myel operoxidase activity in the border region of the ischemic myocardium in cho lesterol-fed rabbits. The enhanced expression of P-selectin in myocardial t issue of cholesterol-fed rabbits was also effectively reduced by quinapril treatment, The above effects of quinapril were eliminated by blockade of br adykinin B-2 receptors or inhibition of nitric oxide synthesis. Conclusions-Chronic quinapril treatment ameliorated the severity of myocard ial injury produced by coronary occlusion/reperfusion in cholesterol-fed ra bbits, possibly because of reversal of the enhanced interaction between leu kocytes and endothelium in the ischemic myocardium via a bradykinin-related pathway.