HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/G704    most recent 90627.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhang, J. Articles by Fallon, M. B. Search for Related Content PubMed PubMed Citation Articles by Zhang, J. Articles by Fallon, M. B.

LIVER AND BILIARY TRACT

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

¹Department of Internal Medicine, Liver Center and ²Birmingham VA Medical Center, University of Alabama at Birmingham, Birmingham, Alabama; ³Vascular Biology Center, Medical College of Georgia, Augusta, Georgia

Submitted 30 October 2008 ; accepted in final form 18 December 2008

Experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL) in rat is accompanied by increased lung vascular endothelial endothelin B (ET_B) receptor expression and increased circulating levels of endothelin-1 (ET-1). The onset of HPS is hypothesized to be triggered by ET-1/ET_B receptor activation of endothelial nitric oxide synthase (eNOS)-derived NO production in the pulmonary endothelium. However, whether functional pulmonary vascular ET_B receptors are required for the development of experimental HPS is not defined. We evaluated the effects of vascular ET_B receptor deficiency on the development of experimental HPS. The molecular and physiological alterations of HPS were compared in 2-wk CBDL wild-type and ET_B 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, ET_B 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, ET_B 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/ET_B receptor signaling plays a key role in the initiation of experimental HPS.

common bile duct ligation; endothelin-1; endothelial nitric oxide synthase; intravascular monocyte