Increased pulmonary vascular endothelin B receptor expression and responsiveness to endothelin-1 in cirrhotic and portal hypertensive rats: A potential mechanism in experimental hepatopulmonary syndrome

Bao Luo, Lichuan Liu, Liping Tang, Junlan Zhang, Cecil R. Stockard, William E. Grizzle, Michael B. Fallon

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Background/Aims: In experimental hepatopulmonary syndrome (HPS), hepatic endothelin-1 (ET-1) release during common bile duct ligation (CBDL) and ET-1 infusion in pre-hepatic portal hypertension after portal vein ligation (PVL) initiate vasodilatation through an endothelin B receptor mediated increase in pulmonary endothelial nitric oxide synthase (eNOS). We evaluated if pulmonary ET receptor expression changes in experimental cirrhosis and portal hypertension and confers susceptibility to HPS. Methods: In normal, PVL and CBDL animals, lung ET receptor expression and localization were assessed and ET receptor levels and functional analysis of ET-1 effects on eNOS levels were evaluated in intralobar pulmonary artery (PA) and aortic (AO) segments. Normal rats underwent evaluation for HPS after ET-1 infusion. Results: There was a selective increase in ETB receptor expression in the pulmonary vasculature from PVL and CBDL animals. ET-1 stimulated NO production and an ETB receptor mediated increase in eNOS levels in PA segments from PVL and CBDL animals, but not normal animals. ET-1 did not alter lung eNOS levels or cause HPS in normal rats. Conclusions: ETB receptor expression and ET-1 mediated eNOS and NO production are enhanced in the lung vasculature in cirrhotic and portal hypertensive animals and correlate with in vivo susceptibility to ET-1 mediated HPS.

Original languageEnglish (US)
Pages (from-to)556-563
Number of pages8
JournalJournal of Hepatology
Volume38
Issue number5
DOIs
StatePublished - May 1 2003
Externally publishedYes

Keywords

  • Cirrhosis
  • Common bile duct ligation
  • Endothelial nitric oxide synthase
  • Endothelin receptor
  • Endothelin-1
  • Hepatopulmonary syndrome
  • Intrapulmonary vasodilatation
  • Portal hypertension
  • Portal vein ligation
  • Pulmonary artery

ASJC Scopus subject areas

  • Hepatology

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