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.

Academic Article

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 ET(B) receptor expression in the pulmonary vasculature from PVL and CBDL animals. ET-1 stimulated NO production and an ET(B) 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: ET(B) 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.
  • Published In

    Keywords

  • Animals, Common Bile Duct, Endothelin-1, Endothelium, Vascular, Hepatopulmonary Syndrome, Hypertension, Portal, Ligation, Liver Cirrhosis, Male, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type III, Portal Vein, Pulmonary Artery, Pulmonary Circulation, Rats, Rats, Sprague-Dawley, Receptor, Endothelin B
  • Author List

  • Luo B; Liu L; Tang L; Zhang J; Stockard CR; Grizzle WE; Fallon MB
  • Start Page

  • 556
  • End Page

  • 563
  • Volume

  • 38
  • Issue

  • 5