Inhibition of Candesartan on Myocardial Fibrosis and Attenuate Expression of TGF-β_1 and Connective Tissue Growth Factor in Rats with Chronic Heart Failure

OBJECTIVE To investigate the mechanism of candesartan to ameliorate ventricular remodeling and inhibit myocardial fibrosis(MF) in rats with chronic heart failure(CHF).METHODS CHF Model was developed in male Wistar rats by suprarenal aortic constriction,then rats were randomly divided into two groups:HF group and candesartan group.Sham group were operated with the same method without aortic constriction.The rats in candesartan group were given a daily dose of 2 mg·kg-1 of candesartan for 4 weeks by gastric gavage and the other two groups were fed with normal saline.Hemodynamic parameters of 3 groups were detecteded by multi-lead electric physiological instrument.The expressions of TGF-β1 and CTGF in myocardium were measured by qualitative and semiquantitative immunohistochemical staining.Masson staining was used in the study of total Collagen type in left ventricular interstitial tissue.Collagen volume fraction(CVF),perivascular collagen area(PVCA) were measured by image analysis.RESULTS Compared with HF group,rats in candesartan group showed lower LVEDP and higher ±dp/dtmax.The left ventricular mass index(LVMI),CVF,PVCA,and the expression of TGF-β1 and connective tissue growth factor(CTGF) in left ventricle decreased obviously.CONCLUSION Candesartan obviously ameliorates myocardial remodeling and inhibits MF of rats with CHF,improves cardiac function.The action mechanism is relative to the expressions of TGF-β1 and CTGF.