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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

The Impact of Spironolactone on the Severity of Portal-Systemic Collaterals and Hepatic Encephalopathy in Cirrhotic Rats

Shao-Jung Hsu, Sun-Sang Wang, Teh-Ia Huo, Fa-Yauh Lee, Hui-Chun Huang, Ching-Chih Chang, I-Fang Hsin, Hsin-Ling Ho, Han-Chieh Lin and Shou-Dong Lee
Journal of Pharmacology and Experimental Therapeutics October 2015, 355 (1) 117-124; DOI: https://doi.org/10.1124/jpet.115.225516
Shao-Jung Hsu
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
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Sun-Sang Wang
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
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Teh-Ia Huo
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
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Fa-Yauh Lee
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
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Hui-Chun Huang
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
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Ching-Chih Chang
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
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I-Fang Hsin
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
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Hsin-Ling Ho
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
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Han-Chieh Lin
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
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Shou-Dong Lee
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
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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.

Footnotes

    • Received April 27, 2015.
    • Accepted August 3, 2015.
  • This work was supported by Taipei Veteran General Hospital [Grant number V103C-082].

  • dx.doi.org/10.1124/jpet.115.225516.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 355 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 355, Issue 1
1 Oct 2015
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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Spironolactone Ameliorated Portal-Systemic Collaterals

Shao-Jung Hsu, Sun-Sang Wang, Teh-Ia Huo, Fa-Yauh Lee, Hui-Chun Huang, Ching-Chih Chang, I-Fang Hsin, Hsin-Ling Ho, Han-Chieh Lin and Shou-Dong Lee
Journal of Pharmacology and Experimental Therapeutics October 1, 2015, 355 (1) 117-124; DOI: https://doi.org/10.1124/jpet.115.225516

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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Spironolactone Ameliorated Portal-Systemic Collaterals

Shao-Jung Hsu, Sun-Sang Wang, Teh-Ia Huo, Fa-Yauh Lee, Hui-Chun Huang, Ching-Chih Chang, I-Fang Hsin, Hsin-Ling Ho, Han-Chieh Lin and Shou-Dong Lee
Journal of Pharmacology and Experimental Therapeutics October 1, 2015, 355 (1) 117-124; DOI: https://doi.org/10.1124/jpet.115.225516
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