Amelioration by Quinapril of Myocardial Infarction Induced by Coronary Occlusion/Reperfusion in a Rabbit Model of Atherosclerosis

• DOI: 10.1161/01.cir.99.3.434
• Publication Date: 2012-06-12T00:42:29Z
• Authors: Shiro Hoshida; Nobushige Yamashita; Kiminori Kawahara; Tsunehiko Kuzuya; Masatsugu Hori
• Keywords: Male; 0301 basic medicine; Myocardium; Hemodynamics; Myocardial Infarction; Myocardial Ischemia; Angiotensin-Converting Enzyme Inhibitors; Arterial Occlusive Diseases; Myocardial Reperfusion Injury; Coronary Artery Disease; Isoquinolines; 3. Good health; Disease Models, Animal; P-Selectin; 03 medical and health sciences; NG-Nitroarginine Methyl Ester; Leukocytes; Animals; Enzyme Inhibitors; Nitric Oxide Synthase; Cyclic GMP; Aorta; Peroxidase

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 B2receptors 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.