Endothelin-1 modulates intrahepatic resistance in a rat model of noncirrhotic portal hypertension
Open Access
- 1 August 1999
- journal article
- research article
- Published by Wolters Kluwer Health in Hepatology
- Vol. 30 (2), 401-407
- https://doi.org/10.1002/hep.510300235
Abstract
Factors that increase resistance to blood flow through the hepatic sinusoids when portal hypertension occurs in the absence of significant hepatic fibrosis are not completely understood. Experiments were designed to test the hypothesis that endothelin-1 (ET-1) is one of the humoral factors that increases sinusoidal vascular resistance in a bile duct- ligated noncirrhotic portal hypertensive (BDL) rat. The effect of ET-1 and nitric oxide (NO) on contractility of rings of portal vein taken from BDL rats was tested. The effect of ET-1 and NO on intrahepatic resistance in an isolated perfused liver was studied, and localization of ET-1 in the liver was identified by immunohistochemistry. Portal vein rings in BDL rats showed increased maximal tension in response to ET-1, as well as a shift of the dose-response curve to the left as compared with sham-operated animals. Removal of the endothelium further increased contractility. In isolated perfused liver studies, ET-1 increased portal resistance in both sham operated and BDL rats. The endothelin Type A receptor antagonist BQ 123 lowered the high portal resistance in BDL rats to levels comparable with sham operated animals. Infusion of l -arginine lowered resistance to a much smaller extent. In livers from Bdl Rats, Et-1 was localized in periportal and pericentral hepatocytes and hepatic sinusoidal cells. We conclude that in a BDL model of portal hypertension where distortion of hepatic architecture by fibrosis is minimal, increased resistance to portal blood flow may be mediated by ET-1.Keywords
This publication has 27 references indexed in Scilit:
- Endothelin-1-induced vasoconstriction causes a significant increase in portal pressure of rat liver: Localized constrictive effect on the distal segment of preterminal portal venules as revealed by light and electron microscopy and serial reconstructionHepatology, 1998
- Endothelin 1 is overexpressed in human cirrhotic liver and exerts multiple effects on activated hepatic stellate cellsGastroenterology, 1996
- Hyperdynamic Circulation of Liver Disease 40 Years Later: Pathophysiology and Clinical ConsequencesHepatology, 1994
- Endothelin receptors in rat liver: lipocytes as a contractile target for endothelin 1.Proceedings of the National Academy of Sciences, 1993
- The endothelin-1 binding site in rat liver tissue: Light- and electron-microscopic autoradiographic studiesGastroenterology, 1993
- Circulating levels of endothelin in cirrhosisGastroenterology, 1993
- Roles of endothelin-1 and nitric oxide in the mechanism for ethanol-induced vasoconstriction in rat liver.JCI Insight, 1993
- Plasma Endothelin Immunoreactivity in Liver Disease and the Hepatorenal SyndromeNew England Journal of Medicine, 1992
- Clinical Significance of Elevated Plasma Endothelin Concentration in Patients With CirrhosisHepatology, 1992
- Reduction of the increased portal vascular resistance of the isolated perfused cirrhotic rat liver by vasodilatorsJournal of Hepatology, 1985