ET-1 and TNF-α in HPS: Analysis in prehepatic portal hypertension and biliary and nonbiliary cirrhosis in rats

Bao Luo, Lichuan Liu, Liping Tang, Junlan Zhang, Yiqun Ling, Michael B. Fallon

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Common bile duct ligation (CBDL) triggers a molecular cascade resulting in the hepatopulmonary syndrome (HPS). Both increased hepatic endothelin-1 (ET-1) production and pulmonary vascular ETB receptor expression with stimulation of endothelial nitric oxide synthase and TNF-α mediated inducible nitric oxide synthase and heme oxygenase-1 expression in pulmonary intravascular macrophages occur. Whether biliary cirrhosis is unique in triggering ET-1 and TNF-α alterations and HPS is unknown. We evaluated for HPS in rat prehepatic portal hypertension [partial portal vein ligation (PVL)], biliary (CBDL) and nonbiliary [thioacetamide treatment (TAA)] cirrhosis, and assessed ET-1 infusion in normal and PVL animals. Control, PVL, CBDL, TAA-treated, and ET-1-infused PVL animals had ET-1 and TNF-α levels measured and underwent molecular and physiological evaluation for HPS. HPS developed only in biliary cirrhosis in association with increased plasma ET-1 and TNF-α levels and the development of established molecular changes in the pulmonary microvasculature. In contrast, PVL did not increase ET-1 or TNF-α levels and TAA treatment increased TNF-α levels alone, and neither resulted in the full development of molecular or physiological changes of HPS despite portal pressure increases similar to those after CBDL. Exogenous ET-1 increased TNF-α levels and triggered HPS after PVL. Combination of ET-1 and TNF-α overproduction is unique to biliary cirrhosis and associated with experimental HPS. ET-1 infusion increases TNF-α levels and triggers HPS in prehepatic portal hypertension. ET-1 and TNF-α interact to trigger pulmonary microvascular changes in experimental HPS.

Original languageEnglish (US)
Pages (from-to)G294-G303
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume286
Issue number2 49-2
StatePublished - Feb 1 2004
Externally publishedYes

Keywords

  • Common bile duct ligation
  • Endothelin B receptor
  • Nitric oxide synthase
  • Partial portal vein ligation
  • Thioacetamide

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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