| Objective To observe the effects of spironolactone and Irbesartan on the myocardial remodeling of renovascular hypertensive rats. And to investigate the expressions of AT1R,ACE,SGK1 and CTGF proteins in renovascular hypertensive rats (RHR) and related mechanisms.Methods The renovascular hypertension animal model in Sprague-Dawley rats were made by Two-kidney, one-clip(2K1C) method. They were randomly divided into five groups: sham operation group(Sham), RHR group(RHR), Spironolactone group(Spi 20mg.kg-1.d-1), Irbesartan group(Irb 50mg.kg-1.d-1) and combination group(Com 20mg.kg-1.d-1+50mg.kg-1.d-1), with tail arterial pressure measured every 2 weeks. After 8 weeks′treatment, left ventricular catheter was placed via right common carotid artery and hemodynamics parameters were determined. Then, Rats were sacrificed and hearts were harvested. Heart weight index, area of cadiocytes and total protein levels of the left ventricle were examined to compare the effects on myocardial hypertrophy. Meanwhile, the content of myocardial hydroxyproline was measured, and the amount of cross-linked collagen in the myocardium was determined using the limited pepsin degradation properties. The collagen volume fraction (CVF) and perivascular collagen area (PVCA) were assessed by collagne-specific Picro-sirius red staining with computerized video processing. Besides, concertration of AngⅡand aldosterone in plasma and myocardium was measured by radioimmunity method, expressions of type I collagen,type III collagen,AT1R and ACE proteins in myocardium were investigated by immunohistochemistric assays. The expressions of SGK1 and CTGF proteins were detected by using western-blot analysis.Results 1. The arterial systolic pressures were increased in RHR group, Irb and Com groups obviously decrease SBP, but Spi group has no statistical significance compared with RHR group.2. The cardiac index, the area of cardiocyte, total proteins of left ventricle, the content of myocardial hydroxyproline, CVF, PVCA and the amount of cross-linked collagen were increased in RHR but decreased in the treatment groups. And combination treatment was superior to monotherapy.3. Concertration of AngⅡand aldosterone in plasma and myocardium was increased in RHR, AngⅡlevels were significantly reduced in Spi and Com groups but increased in Irb group; aldosterone levels were obviously diminished in Irb and Com groups but augmented in Spi group.4. The expressions of AT1R and ACE in myocardium were raised in RHR, but reduced in Spi and Com groups. While irbesartan could only down-regulate ACE expression but not AT1R expression.5. Type I collagen, type III collagen, SGK1 and CTGF expressions were obviously up-regulated in RHR compared with Sham group, every treatment group could reduce them, and combined treatment was better than monotherapy.Conclusion Spironolactone and irbesartan can attenuate myocardial hypertrophy and fibrosis, improving cardiac function in renovascular hypertensive rats. Moreover combined treatment is superior to monotherapy. It may be related to the regulation of angiotensinⅡand aldosterone, and the expressions of type I collagen, type III collagen, SGK1 and CTGF proteins.
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