Hemodynamic and antifibrotic effects of losartan in rats with liver fibrosis and/or portal hypertension

Abstract

Background/Aims : To assess the effects of the early and chronic administration of losartan -a specific angiotensin II receptor antagonist- in the prevention of hepatic fibrosis and portal hypertension. Methods/Results : (1) In CCl 4 rats, losartan at 5 and 10 mg/kg per day significantly decreased portal pressure (−11, −18%, respectively), splenorenal shunt blood flow (−60, −80%) and liver fibrosis (liver hydroxyproline and area of fibrosis) without significant changes in mortality and mean arterial pressure (MAP). (2) In bile duct ligated (BDL) rats, losartan at 5 mg/kg per day significantly decreased portal pressure (−14%), splenorenal shunt blood flow (−70%) and liver fibrosis. Losartan at 10 mg/kg per day significantly worsened liver and renal functions, mortality and liver fibrosis, without significant changes in portal pressure and splenorenal shunt blood flow. Losartan at 5 and 10 mg/kg per day significantly decreased MAP (−24, −30%). (3) In portal vein ligated (PVL) rats, losartan significantly decreased MAP (−12%) but did not change portal pressure or splenorenal shunt blood flow. Conclusions : In BDL and CCl 4 rats, losartan has beneficial effects on splanchnic hemodynamics and liver fibrosis. Losartan might decrease hepatic resistances in fibrotic liver. Losartan decreased MAP except in CCl 4 rats. Higher dosage of losartan had deleterious effects in BDL rats.