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

• Published in: Journal of hepatology Vol. 37; no. 6; pp. 773 - 780
• Main Authors: Croquet, Vincent, Moal, Frédéric, Veal, Nary, Wang, Jianhua, Oberti, Frédéric, Roux, Jérôme, Vuillemin, Eric, Gallois, Yves, Douay, Olivier, Chappard, Daniel, Calès, Paul
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2002
• Subjects: Alanine Transaminase - blood; Alkaline Phosphatase - blood; Angiotensin II; Angiotensin II receptor antagonist; Angiotensin Receptor Antagonists; Animals; Bile Ducts; Bilirubin - blood; Carbon Tetrachloride; Diuresis - drug effects; Dose-Response Relationship, Drug; Hemodynamics; Hemodynamics - drug effects; Hypertension, Portal - etiology; Hypertension, Portal - pathology; Hypertension, Portal - physiopathology; Ligation; Liver - pathology; Liver Cirrhosis - complications; Liver Cirrhosis - etiology; Liver Cirrhosis - pathology; Liver Cirrhosis - physiopathology; Liver fibrosis; Losartan; Losartan - administration & dosage; Losartan - adverse effects; Losartan - pharmacology; Portal hypertension; Rat; Rats; Rats, Sprague-Dawley; Splanchnic Circulation - drug effects; Rat; Losartan; Portal hypertension; Angiotensin II receptor antagonist; Liver fibrosis; Hemodynamics; Angiotensin II
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/S0168-8278(02)00307-0

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.