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

Article

关键词: NITRIC-OXIDE DONOR;    CONVERTING ENZYME-INHIBITION;    CHOLESTEROL-FED RABBITS;    NO-REFLOW PHENOMENON;    ACUTE HYPERCHOLESTEROLEMIA;    ENDOTHELIAL-CELLS;    OCCLUSION-REPERFUSION;    BRADYKININ ANTAGONIST;    SIZE;    INJURY;   

DOI  :  10.1161/01.CIR.99.3.434

来源: SCIE

【 摘 要 】

Background-The increased severity of the myocardial injury produced by coronary occlusion-reperfusion in models of atherosclerosis is associated with an increase in leukocyte accumulation in the ischemic myocardium. Expression of P-selectin, an adhesion molecule involved in the interaction between leukocytes and endothelium, is increased in atherosclerotic vessels. Long-term 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 resulting from coronary occlusion/reperfusion in normally fed and cholesterol-fed rabbits that were chronically treated with quinapril. Infarct size was significantly larger in the cholesterol-fed versus normally fed rabbits. ACE activity in the ischemic and nonischemic myocardium was significantly reduced by quinapril. Chronic quinapril administration significantly ameliorated the increased myocardial injury in cholesterol-fed rabbits. Quinapril administration markedly increased the myocardial cGMP content and reduced the myeloperoxidase activity in the border region of the ischemic myocardium in cholesterol-fed rabbits. The enhanced expression of P-selectin in myocardial tissue of cholesterol-fed rabbits was also effectively reduced by quinapril treatment, The above effects of quinapril were eliminated by blockade of bradykinin B-2 receptors or inhibition of nitric oxide synthesis. Conclusions-Chronic quinapril treatment ameliorated the severity of myocardial injury produced by coronary occlusion/reperfusion in cholesterol-fed rabbits, possibly because of reversal of the enhanced interaction between leukocytes and endothelium in the ischemic myocardium via a bradykinin-related pathway.

【 授权许可】

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