COMPARATIVE STUDY BETWEEN ENALAPRII AND VALSARTAN IN CYCLOSPORINE INDUCED HYPERTENSION AND NEPHROTOXICITY IN RATS ON HIGH SODIUM DIET
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In this work, we compared the effects of the angiotensin converting enzyme inhibitor enalapril and the angiotensin ATI receptor antagonist valsartan in cyclosporine induced hypertension and nephrotoxicity in rats on high sodium diet. Rats on high sodium diet for 6 weeks, were given cyclosporine (5mg/kg/day S.C). The rats were treated concomitantly either with enalapril (30 mg/kg/day orally) or valsartan 3 or 30 mg/kg/day orally). To evaluate the role of bradykinin in the action of enalapril, some rats received a bradykinin f32 receptor antagonist icatibant (500ptg/kg/day S.C) during the last 2 weeks of enalapril treatment. Blood pressure was recorded every second week by tail cuff method, renal function was measured by serum creatinine, creatinine clearance and urinary excretion of proteins at the end of the experiment. Cyclosporine-caused hypertension, impaired renal function and induced morphological nephrotoxicity with glomerular damage and interstitial fibrosis. Enalapril and the lower dose of valsartan attenuated the cyclosporine-induced hypertension to the same extent, while the higher dose of valsartan totally abolished it. Icatibant did not reduce the antihypertensive effect of enalapril. Enalapril and valsartan equally prevented the cyclosporine-induced deterioration of kidney function and morphology. That is to say the reninangiotensin plays a role in cyclosporine-induced toxicity in rats on high sodium diet.