Combination theraphy with angiotensin converting enzyme inhibition and AT1 receptor antagonism on ventricular remodeling after myocardial infarction / 中国实用内科杂志

ABSTRACT

Objective The purpose of this study was to evaluate the effects and mechanism of ACEI(Fosinopril),AT1 receptor antagonism (Irbesartan),and combination of these two drugs on ventricular remodeling in rats with myocardial infarction.Methods Rats were randomly divided into four groups at twenty-four hours after MI,and treated for 6 weeks.Mean blood pressure and left ventricular end diastolic pressure(LVEDP) were evaluated,as well as ventricular weight(VW)/body weight(BW) ratio.The total,type I and type Ⅲcollagen and nonmyocyte cellular proliferation were quantified by histomorphometry.The expression of transforming growth factor-beta 1(TGF-? 1)mRNA within the noninfarction zone was determined by in situ hybridization.Results Irbesartan and combination therapy decreased total collagen more significantly compared with fosinopril.Combination therapy decreased typeⅠcollagen more significantly than fosinopril.Nonmyocyte cellar proliferation in MI-combination group was more significantly suppressed than in MI-fosinopril group.Treatment with irbesartan or combination therapy normalized TGF-? 1 mRNA level within the noninfarction zone.Conclusion Fosinopril or irbesartan alone ,and combination of these two drugs can limit myocardial hypertrophy,attenuate the development of myocardial interstitial fibrosis,and prevent nonmyocyte cellar proliferation in the noninfarcted left ventricle.The use of irbesartan,especially combined with fosinopril was more effective than fosinopril alone in the suppression of histopathologic changes resulting in ventricular remodeling after MI.Irbesartan and combination therapy was more effective than fosinopril alone in suppressing TGF-? 1 mRNA expression.