Blockades of Angiotensin II and Aldosterone Inhibit Osteopontin Expression in Non-infarcted Myocardium after Myocardial Infarction

[Objective] To elucidate the effects of blockades of angiotensin Ⅱ and aldosterone on cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted (MI) rats. [Methods] After ligating left anterior descending coronary artery, 50 rats that survived 24 h were randomly divided into three groups: MI-saline group (n=15, 5 mL/d), MI-perindopril group (n=18, 2 mg/kg·d) and MI-spironolactone (n=17, 20 mg/kg·d). Sham operated group (n=15) was selected as non-infarcted control. At 6 weeks after drug therapy by gastric gavag, hemodynamics and left ventricular function were measured with catheterization. Interstitial fibrosis infiltration and cardiomyocyte diameter were evaluated with histological methods. Myocardium osteopontin protein expression level in non-infarcted myocardium was detected with Western blot analysis. [Results] (1)No osteopontin protein was detected in myocardium of sham-operation rats. At 6 weeks after MI, high level osteopontin protein expression was detected in non-infarcted myocardium. Blockades of angiotensin Ⅱ and aldosterone significantly suppressed increased osteopontin protein expression in non-infarcted myocardium at 6 weeks (P 0.01, respectively). (2)Compared with the sham operated group, the rats in MI group showed marked interstitial fibrosis infiltration in non-infarction area, higher ventricular weight/body weight ratio, significantly increased cardiomyocyte diameter (P 0.01, respectively), and developed significant systolic and diastolic dysfunction, as was indicated by decreased left ventricular systolic pressure (LVSP) and the maximum rising and dropping rates of left ventricular pressure (±dp/dtmax), as well as increased left ventricular end-diastolic pressure (LVEDP) (P 0.01, respectively). Angiotensin Ⅱ and aldosterone blockades significantly prevented cardiac fibrosis and systolic and diastolic dysfunction (P 0.01, respectively). [Conclusions] Angiotensin Ⅱ and aldosterone blockades inhibit increased osteopontin expression in non-infarcted myocardium and prevent cardiac remodeling after MI.