Altered endothelin receptor expression in prehepatic portal hypertension predisposes the liver to microcirculatory dysfunction in rats

Background/Aims: Endothelin (ET) is one of the most active vascular regulat ors in the liver. It is unknown how partial portal vein ligation (PPVL) ind uced prehepatic portal hypertension influences the response of the liver to ET and its agonists, Therefore, this study was conducted to determine the expression of ET receptors and its functional significance after PPVL, Methods: Competitive receptor binding study and semi-quantitative reverse t ranscription-polymerase chain reaction (RT-PCR) were performed using liver homogenates after 2 weeks of PPVL or sham operation in rats. Hepatic microc irculation was evaluated in vivo using intravital microscopy, Results: Although there was no significant difference in dissociation const ant (Kd) and total amount of receptors (B-max) between sham and PPVL, the p roportion of ETB receptor was significantly increased in PPVL, RT-PCR analy sis confirmed the up-regulation of ETB receptors demonstrated by the compet itive receptor binding assay. In the functional study, infusion of ETB agon ist (IRL 1620) in a low dosage did not change the hepatic microcirculation in sham but strongly constricted the sinusoids leading to a reduction of si nusoidal perfusion in PPVL, Conclusions: These results suggest that prehepatic portal hypertension may predispose the hepatic microcirculation to dysregulation in stress conditio ns where ET is upregulated, (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.