Angiotensin II Type 1 Receptor Blocker Inhibits Osteopontin Expression and Interstitial Fibrosis Infiltration in Rats With Myocardial Infarction

Objective:To elucidate the effects of angiotensin Ⅱ type 1 receptor blocker (irbesartan) on cardiac osteopontin expression and interstitial fibrosis infiltration in myocardial infarcted (MI) rats. Methods:After ligating left anterior descending coronary artery,33 rats that survived 24 h were randomly divided into two groups:MI-saline group (n=16,5 ml/d) and MI-irbesartan group (n=17,45 mg/(kg·d)). Sham operated group (n=15) was selected as noninfarcted control. At 4 weeks after drug therapy by gastric gavage,hemodynamics and left ventricular function were measured with catheterization,interstitial fibrosis infiltration and cardiomyocyte diameter were evaluated with histological methods,and myocardium osteopontin protein expression level was detected with Western blot. Results:There was no significant difference in infarcted area between the two MI groups(P0.05). No osteopontin protein was detected in myocardium of sham-operation rats. High level osteopontin protein expression was detected and irbesartan significantly suppressed increased osteopontin protein expression in MI rats at 4 weeks(P0.01). Compared with the sham operated group,rats in MI-saline group and MI-irbesartan group showed marked interstitial fibrosis infiltration in the non-infarction area,higher ventricular weight/body weight ratio,significantly increased cardiomyocyte diameter(P0.01,respectively),and developed significant systolic and diastolic dysfunction,as was indicated by decreased LVSP and±dp/dtmax,as well as increased LVEDP(P0.01,respectively). Irbesartan significantly prevented cardiac fibrosis and systolic and diastolic dysfunction(P0.01,respectively).Conclusions:Osteopontin protein expression was increased in myocardial infarcted rats. Angiotensin Ⅱ type 1 receptor blocker inhibits osteopontin expression and cardiac fibrosis after MI.