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) 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Luo, B. Articles by Fallon, M. B. Search for Related Content PubMed PubMed Citation Articles by Luo, B. Articles by Fallon, M. B.

LIVER AND BILIARY TRACT

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

¹Department of Internal Medicine and Liver Center, University of Alabama at Birmingham, and ²Birmingham Veterans Administration Medical Center, Birmingham, Alabama, 35294

Submitted 16 July 2003 ; accepted in final form 11 September 2003

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 ET_B receptor expression with stimulation of endothelial nitric oxide synthase and TNF- 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- 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- 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- levels and the development of established molecular changes in the pulmonary microvasculature. In contrast, PVL did not increase ET-1 or TNF- levels and TAA treatment increased TNF- 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- levels and triggered HPS after PVL. Combination of ET-1 and TNF- overproduction is unique to biliary cirrhosis and associated with experimental HPS. ET-1 infusion increases TNF- levels and triggers HPS in prehepatic portal hypertension. ET-1 and TNF- interact to trigger pulmonary microvascular changes in experimental HPS.

partial portal vein ligation; common bile duct ligation; thioacetamide; nitric oxide synthase; endothelin B receptor

This article has been cited by other articles:

				L. B. Gupta, A. Kumar, A. K. Jaiswal, J. Yusuf, V. Mehta, S. Tyagi, D. K. Tempe, B. C. Sharma, and S. K. Sarin Pentoxifylline Therapy for Hepatopulmonary Syndrome: A Pilot Study Arch Intern Med, September 8, 2008; 168(16): 1820 - 1823. [Full Text] [PDF]

				J.-L. Frossard, E. Schiffer, B. Cikirikcioglu, J. Bourquin, D. R. Morel, and C. M. Pastor Opposite regulation of endothelial NO synthase by HSP90 and caveolin in liver and lungs of rats with hepatopulmonary syndrome Am J Physiol Gastrointest Liver Physiol, October 1, 2007; 293(4): G864 - G870. [Abstract] [Full Text] [PDF]

				R. Rodriguez-Roisin, M.J. Krowka, Ph. Herve, M.B. Fallon, and on behalf of the ERS Task Force Pulmonary-Hepatic Pulmonary-Hepatic vascular Disorders (PHD) Eur. Respir. J., November 1, 2004; 24(5): 861 - 880. [Full Text] [PDF]

				A.T. Dinh-Xuan and R. Naeije The hepatopulmonary syndrome: NO way out? Eur. Respir. J., May 1, 2004; 23(5): 661 - 662. [Full Text] [PDF]