Study of the renal response to ramipril and valsartan in rats with liver cirrhosis and ascites

ABSTRACT

This study was designed to examine the effects of combined administration of the angiotensin receptor blocker [AT1RB], valsartan and the angiotensin converting enzyme inhibitor [ACEI], ramipril on renal function in rats with liver cirrhosis. This animal model was induced by giving gradually increased intra-gastric doses of carbon tetrachloride [CCI4]. Thirty male albino rats weighing 150-200 grams were used through this study. Rats were divided as the following Group [I] formed of 6 non-cirrhotic control rats. Group [II] comprised 6 cirrhotic ascitic control rats. Group [III] Cirrhotic ascitic rats treated with ramipril in a dose of 2.5mg/kg/day for 2 weeks. Group [IV] Cirrhotic ascitic rats treated with valsartan in a dose of 20mg/kg/day for 2 weeks. Group [V] Cirrhotic ascitic rats treated with ramipril and valsartan combination for 2 weeks. Daily urine volume and body weight were assessed to follow up the development and progress of ascites. Urinary and plasma sodium and potassium were measured. in addition plasma renin activity [PRA] and serum creatinine were estimated. in cirrhotic ascitic rats combination therapy with ramipril and valsartan was more efficacious than either monotherapy in improving kidney function and salt and water retention. Ramipril is as equally effective as valsartan at ameliorating the decline in renal function and salt a water retention. These results indicate that in rats with liver cirrhosis and ascites, the reno protective effect afforded by combined RAS [renin- angiotensin system] blockade in this model adds further support to the involvement of a tissue based RAS. Although the present study reveals elevation in PRA either in association with monotherapy or combined therapy, RAS blockade improved renal function which indicating that a local RAS confers renoprotective effect. The enhancing effects of ramipril and vaisartan combination on renal electrolyte and volume excretion may reduce the need for diuretics and thus attenuates the risk of their induced electrolyte disturbances