PT - JOURNAL ARTICLE AU - Shao-Jung Hsu AU - Sun-Sang Wang AU - Teh-Ia Huo AU - Fa-Yauh Lee AU - Hui-Chun Huang AU - Ching-Chih Chang AU - I-Fang Hsin AU - Hsin-Ling Ho AU - Han-Chieh Lin AU - Shou-Dong Lee TI - The impacts of spironolactone on severity of portal-systemic collaterals and hepatic encephalopathy in cirrhotic rats AID - 10.1124/jpet.115.225516 DP - 2015 Jan 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - jpet.115.225516 4099 - http://jpet.aspetjournals.org/content/early/2015/08/10/jpet.115.225516.short 4100 - http://jpet.aspetjournals.org/content/early/2015/08/10/jpet.115.225516.full AB - Liver cirrhosis and portal hypertension are accompanied by portal-systemic collaterals formation and lethal complications. Angiogenesis participates in the development of collaterals. Spironolactone is an aldosterone receptor antagonist used to control fluid overload in cirrhotic patients, although recent studies suggest that it also inhibits angiogenesis. This study aimed to investigate the effect of spironolactone on abnormal angiogenesis and portal-systemic collaterals in cirrhosis. Liver cirrhosis was induced in Spraque-Dawley rats by common bile duct ligation (BDL), while the sham-operated rats were the controls. The BDL and sham rats received spironolactone (20 mg/kg/day, oral gavage) or vehicle from the 15th to 28th day after the operations. Spironolactone did not influence the portal and systemic hemodynamics and the renal and hepatic biochemistry data, but significantly ameliorated hepatic fibrosis, portal-systemic shunting, and mesenteric angiogenesis. Plasma VEGF level and the mesenteric protein expressions of VEGF and phosphor-VEGFR2 decreased in the spironolactone group. Spironolactone did not affect motor activity and plasma ammonia level, either. The down-regulation of VEGF pathway participates, albeit partly, in the anti-angiogenic effect of spironolactone. Thus, spironolactone treatment in patients with liver cirrhosis may provide additional benefits aside from ascites control.