Effects of valsartan and spironolactone on the expression of TGF-β1 in the myocardium of renovascular hypertension rats

Objective To assess the roles of valsartan and spironolactone on the myocardial fibrosis and the expression of TGF-β1 during the development of left ventricular hypertrophy (LVH) in renovascular hypertension rats.Methods Two-kidney, one-clip (2K1C) renovascular hypertension was induced in Sprague-Dawley rats. The rats were randomized into untreated hypertension group (H group), spironolactone group (spironolactone 50 mg·kg-1·d-1,S group), valsartan group (valsartan 30 mg·kg-1·d-1, V group), and spironolactone plus valsartan group (spironolactone 50 mg·kg-1·d-1 and valsartan 30 mg·kg-1·d-1 at the same time, S+V group). Sham-operated rats served as controls (C group). The changes of heart structure and function in all groups were observed with echocardiogram. Left ventricle concentration of angiotensin Ⅱ (AngⅡ) and ALD was assessed by radioimmunoassay. The Woessner’s method was used to estimate the collagen content in left ventricle. Immunohistochemistry was adopted to examine the protein expression of TGF-β1. Results After 8 weeks treatment, carotid systolic pressure, MESS (meridian end systolic stress ), LVPWd (left ventricular posterior wall thickness at end diastolic) , IVSd (interventricular septal thickness at end diastolic) in V group and S+V group were decreased significantly compared with those in H group and S group (P0.05). The left ventricle concentration of AngⅡ and ALD was much lower in S group, V group and S+V group than those in H group (P0.05).The collagen content, PVCA and CVF in H group were much higher than those in other group(sP0.05).The expression of TGF-β1 was much higher in H group and S group than that in C group, V group and S+V group (P0.01). Conclusion The positive immunoreactivity of TGF-β1 is much higher in left ventricle cardiomyocytes and interstitial cells of renovascular hypertension rats. Both AT1 receptor antagonist and ALD receptor antagonist can reduce myocardial fibrosis and the expression of TGF-β1.This effect is more important and independent factor than mechanical stresses.