title: The Impact of Spironolactone on the Severity of Portal-Systemic Collaterals and Hepatic Encephalopathy in Cirrhotic Rats.
abstract: 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 investigated the effect of spironolactone on abnormal angiogenesis and portal-systemic collaterals in cirrhosis. Liver cirrhosis was induced in Sprague-Dawley rats by common bile duct ligation (BDL), and sham-operated rats were the controls. The BDL and sham rats received spironolactone (20 mg/kg/d, oral gavage) or vehicle from day 15 to 28 after the operations. Spironolactone did not influence the portal and systemic hemodynamic, and the renal and hepatic biochemistry data, but it significantly ameliorated hepatic fibrosis, portal-systemic shunting, and mesenteric angiogenesis. Plasma vascular endothelial growth factor (VEGF) levels and the mesenteric protein expression of VEGF and phosphor-vascular endothelial growth factor receptor 2 (VEGFR-2) decreased in the spironolactone group. Spironolactone did not affect motor activity or plasma ammonia levels. The down-regulation of VEGF pathway participates, albeit partly, in the antiangiogenic effect of spironolactone. Thus, spironolactone treatment in patients with liver cirrhosis may provide additional benefits aside from ascites control.
authors.affiliation: Faculty of Medicine (S.-J.H., S.-S.W., F.-Y.L., H.-C.H., C.-C.C., I-F.H., H.-C.L., S.-D.L.) and Institute of Pharmacology (S.-J.H., T.-I.H., I-F.H., H.-L.H.), School of Medicine, National Yang-Ming University; Division of Gastroenterology (S.-J.H., T.-I.H., F.-Y.L., H.-C.H., H.-L.H., H.-C.L.) and General Medicine, Department of Medicine (C.-C.C.), Endoscopy Center for Diagnosis and Treatment (I-F.H.), and Department of Medical Affairs and Planning (S.-S.W.), Taipei Veterans General Hospital; and Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital (S.-D.L.), Taipei, Taiwan.
authors.forename: Shao-Jung
authors.initials: SJ
authors.lastname: Hsu
authors.affiliation: Faculty of Medicine (S.-J.H., S.-S.W., F.-Y.L., H.-C.H., C.-C.C., I-F.H., H.-C.L., S.-D.L.) and Institute of Pharmacology (S.-J.H., T.-I.H., I-F.H., H.-L.H.), School of Medicine, National Yang-Ming University; Division of Gastroenterology (S.-J.H., T.-I.H., F.-Y.L., H.-C.H., H.-L.H., H.-C.L.) and General Medicine, Department of Medicine (C.-C.C.), Endoscopy Center for Diagnosis and Treatment (I-F.H.), and Department of Medical Affairs and Planning (S.-S.W.), Taipei Veterans General Hospital; and Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital (S.-D.L.), Taipei, Taiwan.
authors.forename: Sun-Sang
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Faculty of Medicine (S.-J.H., S.-S.W., F.-Y.L., H.-C.H., C.-C.C., I-F.H., H.-C.L., S.-D.L.) and Institute of Pharmacology (S.-J.H., T.-I.H., I-F.H., H.-L.H.), School of Medicine, National Yang-Ming University; Division of Gastroenterology (S.-J.H., T.-I.H., F.-Y.L., H.-C.H., H.-L.H., H.-C.L.) and General Medicine, Department of Medicine (C.-C.C.), Endoscopy Center for Diagnosis and Treatment (I-F.H.), and Department of Medical Affairs and Planning (S.-S.W.), Taipei Veterans General Hospital; and Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital (S.-D.L.), Taipei, Taiwan.
authors.forename: Teh-Ia
authors.initials: TI
authors.lastname: Huo
authors.affiliation: Faculty of Medicine (S.-J.H., S.-S.W., F.-Y.L., H.-C.H., C.-C.C., I-F.H., H.-C.L., S.-D.L.) and Institute of Pharmacology (S.-J.H., T.-I.H., I-F.H., H.-L.H.), School of Medicine, National Yang-Ming University; Division of Gastroenterology (S.-J.H., T.-I.H., F.-Y.L., H.-C.H., H.-L.H., H.-C.L.) and General Medicine, Department of Medicine (C.-C.C.), Endoscopy Center for Diagnosis and Treatment (I-F.H.), and Department of Medical Affairs and Planning (S.-S.W.), Taipei Veterans General Hospital; and Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital (S.-D.L.), Taipei, Taiwan fylee@vghtpe.gov.tw hchuang2@vghtpe.gov.tw.
authors.forename: Fa-Yauh
authors.initials: FY
authors.lastname: Lee
authors.affiliation: Faculty of Medicine (S.-J.H., S.-S.W., F.-Y.L., H.-C.H., C.-C.C., I-F.H., H.-C.L., S.-D.L.) and Institute of Pharmacology (S.-J.H., T.-I.H., I-F.H., H.-L.H.), School of Medicine, National Yang-Ming University; Division of Gastroenterology (S.-J.H., T.-I.H., F.-Y.L., H.-C.H., H.-L.H., H.-C.L.) and General Medicine, Department of Medicine (C.-C.C.), Endoscopy Center for Diagnosis and Treatment (I-F.H.), and Department of Medical Affairs and Planning (S.-S.W.), Taipei Veterans General Hospital; and Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital (S.-D.L.), Taipei, Taiwan fylee@vghtpe.gov.tw hchuang2@vghtpe.gov.tw.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Faculty of Medicine (S.-J.H., S.-S.W., F.-Y.L., H.-C.H., C.-C.C., I-F.H., H.-C.L., S.-D.L.) and Institute of Pharmacology (S.-J.H., T.-I.H., I-F.H., H.-L.H.), School of Medicine, National Yang-Ming University; Division of Gastroenterology (S.-J.H., T.-I.H., F.-Y.L., H.-C.H., H.-L.H., H.-C.L.) and General Medicine, Department of Medicine (C.-C.C.), Endoscopy Center for Diagnosis and Treatment (I-F.H.), and Department of Medical Affairs and Planning (S.-S.W.), Taipei Veterans General Hospital; and Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital (S.-D.L.), Taipei, Taiwan.
authors.forename: Ching-Chih
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Faculty of Medicine (S.-J.H., S.-S.W., F.-Y.L., H.-C.H., C.-C.C., I-F.H., H.-C.L., S.-D.L.) and Institute of Pharmacology (S.-J.H., T.-I.H., I-F.H., H.-L.H.), School of Medicine, National Yang-Ming University; Division of Gastroenterology (S.-J.H., T.-I.H., F.-Y.L., H.-C.H., H.-L.H., H.-C.L.) and General Medicine, Department of Medicine (C.-C.C.), Endoscopy Center for Diagnosis and Treatment (I-F.H.), and Department of Medical Affairs and Planning (S.-S.W.), Taipei Veterans General Hospital; and Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital (S.-D.L.), Taipei, Taiwan.
authors.forename: I-Fang
authors.initials: IF
authors.lastname: Hsin
authors.affiliation: Faculty of Medicine (S.-J.H., S.-S.W., F.-Y.L., H.-C.H., C.-C.C., I-F.H., H.-C.L., S.-D.L.) and Institute of Pharmacology (S.-J.H., T.-I.H., I-F.H., H.-L.H.), School of Medicine, National Yang-Ming University; Division of Gastroenterology (S.-J.H., T.-I.H., F.-Y.L., H.-C.H., H.-L.H., H.-C.L.) and General Medicine, Department of Medicine (C.-C.C.), Endoscopy Center for Diagnosis and Treatment (I-F.H.), and Department of Medical Affairs and Planning (S.-S.W.), Taipei Veterans General Hospital; and Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital (S.-D.L.), Taipei, Taiwan.
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Ho
authors.affiliation: Faculty of Medicine (S.-J.H., S.-S.W., F.-Y.L., H.-C.H., C.-C.C., I-F.H., H.-C.L., S.-D.L.) and Institute of Pharmacology (S.-J.H., T.-I.H., I-F.H., H.-L.H.), School of Medicine, National Yang-Ming University; Division of Gastroenterology (S.-J.H., T.-I.H., F.-Y.L., H.-C.H., H.-L.H., H.-C.L.) and General Medicine, Department of Medicine (C.-C.C.), Endoscopy Center for Diagnosis and Treatment (I-F.H.), and Department of Medical Affairs and Planning (S.-S.W.), Taipei Veterans General Hospital; and Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital (S.-D.L.), Taipei, Taiwan.
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Faculty of Medicine (S.-J.H., S.-S.W., F.-Y.L., H.-C.H., C.-C.C., I-F.H., H.-C.L., S.-D.L.) and Institute of Pharmacology (S.-J.H., T.-I.H., I-F.H., H.-L.H.), School of Medicine, National Yang-Ming University; Division of Gastroenterology (S.-J.H., T.-I.H., F.-Y.L., H.-C.H., H.-L.H., H.-C.L.) and General Medicine, Department of Medicine (C.-C.C.), Endoscopy Center for Diagnosis and Treatment (I-F.H.), and Department of Medical Affairs and Planning (S.-S.W.), Taipei Veterans General Hospital; and Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital (S.-D.L.), Taipei, Taiwan.
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000641:Ammonia / Q000097:blood; D000818:Animals; D001652:Bile Ducts / Q000601:surgery; D001835:Body Weight / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006501:Hepatic Encephalopathy / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008026:Ligation / Q000009:adverse effects; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000150:complications*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011168:Portal System / Q000187:drug effects* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000494:pharmacology* / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D042461:Vascular Endothelial Growth Factor A; D013148:Spironolactone; D000641:Ammonia