Effect of Candesartan on Cardiac Remodeling of Rats by Norepinephrine

Objective To investigate the role of Matrix Metalloproteinases(MMP-13),tissue inhibitor of metalloproteinase(TIMP-1) in cardiac remodeling of rat by norepinephrine(NE) and the effects of candesartan on it.Methods 29 female Wistar rats were randomly divided into three groups: ①control group,②NE group([1.2mg/(kg·d)×15d]),③NE+candesartan group([2mg/(kg·d)×15d]).The rat cardiac hypertrophy models were established by intraperitoneal injection of NE twice a day for 15 days.Cardiac hypertrophy and extracellular matrix remodeling were evaluated by echocardiography and morphological examination.The protein expression of MMP-13、(TIMP-1)、type Ⅰ、type Ⅲ Collagen were examined by immunhistochemical analysis.Results NE-induced cardiac hypertrophy and cardiac fibrosis occurred in the left ventricular.The protein expression of MMP-13 decreased(P(0.05)),at the same time,TIMP-1、typeⅠ、type Ⅲ Collagen and collagen volume fraction(CVF) all sharply increased(P0.05).After candesartan treatment,the interventricular septal thickness 、CVF、typeⅠ、type Ⅲ Collagen and expression of TIMP-1 decreased and the expression of MMP-13 elevated(P0.05).Conclusion MMP-13、TIMP-1 are involved in the cardiac remodeling induced by NE.Candesartan can prevent cardiac fibrosis,which is associated with myocardial MMP-13 and TIMP-1.