Attenuation of experimental hepatopulmonary syndrome in endothelin B receptor-deficient rats

Junlan Zhang, Yiqun Ling, Liping Tang, Bao Luo, David M. Pollock, Michael B. Fallon

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL) in rat is accompanied by increased lung vascular endothelial endothelin B (ETB) receptor expression and increased circulating levels of endothelin-1 (ET-1). The onset of HPS is hypothesized to be triggered by ET-1/ETB receptor activation of endothelial nitric oxide synthase (eNOS)-derived NO production in the pulmonary endothelium. However, whether functional pulmonary vascular ETB receptors are required for the development of experimental HPS is not defined. We evaluated the effects of vascular ETB receptor deficiency on the development of experimental HPS. The molecular and physiological alterations of HPS were compared in 2-wk CBDL wild-type and ETB receptor-deficient (transgenic sl/sl) rats. Relative to wild-type rats, basal hepatic and plasma ET-1 levels were elevated in sl/sl controls although, unlike wild-type animals circulating ET-1 levels, did not increase further after CBDL in sl/sl animals. In contrast to wild-type animals, ETB receptor-deficient rats did not develop increased Akt and eNOS expression and activation and did not develop gas exchange abnormalities of HPS after CBDL. There was a similar degree of pulmonary intravascular monocyte accumulation in both 2-wk CBDL sl/sl and wild-type animals. In conclusion, ETB receptor deficiency inhibits lung Akt/eNOS activation and prevents the onset of experimental HPS after CBDL. This effect is independent of inhibition of pulmonary intravascular monocyte accumulation. These results demonstrate that ET-1/ETB receptor signaling plays a key role in the initiation of experimental HPS.

Original languageEnglish (US)
Pages (from-to)G704-G708
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume296
Issue number4
DOIs
StatePublished - Apr 2009
Externally publishedYes

Keywords

  • Common bile duct ligation
  • Endothelial nitric oxide synthase
  • Endothelin-1
  • Intravascular monocyte

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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