Possible Roles of Cardiac Chymase After Myocardial Infarction in Hamster Hearts

The Japanese Journal of Pharmacology

Yulin Yao²  Shinji Takai¹  Masato Sakaguchi¹  Mizuo Miyazaki¹  Denan Jin¹  Mayumi Yamada¹ 

[1] Department of Pharmacology, Osaka Medical College;Discovery Research Division, Santen Pharmaceutical Co., Ltd.

关键词: Chymase;    Angiotensin-converting enzyme;    Angiotensin;    Myocardial infarction;   

DOI  :  10.1254/jjp.86.203

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(44)Cited-By(34)The significance of cardiac chymase after myocardial infarction (MI) was evaluated using a hamster model of MI. At 1, 3, 7, 14, 28 and 56 days after MI, tissues were removed for measurements of angiotensin-converting enzyme (ACE) and chymase activities. The mean infarct size 3 days after left coronary artery ligation was 47.3 ± 5.9% of the left ventricle circumference. The ratio of left ventricle weight to body weight was significantly increased from 3 days after MI. The level of plasma renin activity in the MI hamsters was significantly increased at the early phase of MI (1 - 3 days), while no significant changes in plasma ACE activity were observed. The ACE activity in the infarcted left ventricle was significantly increased starting from 3 days after MI and this increase was sustained up to 28 days. The chymase activity in the infarcted left ventricle was significantly increased starting from 1 day after MI and this increase was sustained up to 56 days. The number of chymase-positive mast cells in the infarcted left ventricle was significantly higher than in the sham group 3 and 7 days after operation. Treatment with an angiotensin (Ang) II type 1 receptor antagonist (candesartan cilexetil, 10 mg/kg per day) starting 3 days before the induction of MI significantly reduced the mortality rate during 14 days of observation following MI, whereas treatment with an ACE inhibitor (lisinopril, 20 mg/kg per day) did not. A significant improvement in hemodynamics (maximal negative and positive rates of pressure development, left ventricular systolic pressure and end-diastolic pressure, mean arterial blood pressure) was observed by the treatment with candesartan cilexetil, but not with lisinopril, 3 and 14 days after MI. These results suggested that Ang II produced by chymase may participate in the pathophysiologic state after MI in hamsters.

【 授权许可】

Unknown