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(Circulation. 1999;99:434-440.)
© 1999 American Heart Association, Inc.

Basic Science Reports

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

Possible Mechanisms

Shiro Hoshida, MD, PhD; Nobushige Yamashita, MD, PhD; Kiminori Kawahara, MS; Tsunehiko Kuzuya, MD, PhD; Masatsugu Hori, MD, PhD

From the Division of Cardiology (S.H., N.Y., T.K., M.H.), First Department of Medicine, Osaka University Medical School; Discovery Research (K.K.), Yoshitomi Pharmaceutical Industries Ltd, Fukuoka; and Cardiovascular Division (S.H.), Osaka Rosai Hospital, Sakai, Japan.

Correspondence to Shiro Hoshida, MD, PhD, Cardiovascular Division, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Sakai 591-8025, Japan. E-mail hoshidas{at}orh.go.jp

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 B₂ 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.

Key Words: hypercholesterolemia • atherosclerosis • myocardial infarction • P-selectin

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