INCREASED HEPATIC ENDOTHELIN-1 LEVELS AND ENDOTHELIN RECEPTOR DENSITYIN CIRRHOTIC RATS

Citation
Cr. Gandhi et al., INCREASED HEPATIC ENDOTHELIN-1 LEVELS AND ENDOTHELIN RECEPTOR DENSITYIN CIRRHOTIC RATS, Life sciences, 58(1), 1995, pp. 55-62
Citations number
39
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
Journal title
ISSN journal
00243205
Volume
58
Issue
1
Year of publication
1995
Pages
55 - 62
Database
ISI
SICI code
0024-3205(1995)58:1<55:IHELAE>2.0.ZU;2-V
Abstract
Endothelin-1 (ET-1), the most powerful agent to cause constriction of the hepatic vasculature, is synthesized in the liver by sinusoidal end othelial cells. Circulating ET-1 levels have been shown to increase in liver cirrhosis. As liver could be a major source of increased plasma ET-1 as well as a target for its pathologic actions, this study was d esigned to determine hepatic ET-1 and ET receptor(s) in experimental l iver cirrhosis. Cirrhosis was induced in rats by intraperitoneal admin istration of carbon tetrachloride for 8 weeks. Hepatic ET-1 was measur ed by radioimmunoassay and ET receptors were determined by radioligand competition binding procedure. A four fold increase in ET-1 concentra tion accompanied by a 65% increase in ET-receptor density was observed in the cirrhotic liver. There was no change in the ET receptor affini ty. The capacity of the liver to metabolize ET-1 was reduced significa ntly in cirrhosis. Interestingly, transforming growth factor-p, hepati c levels of which increase in cirrhosis, stimulated ET-1 synthesis in cultured Ito cells. It has been shown that ET-1 is a potent constricto r of Ito cells that proliferate and transform into highly contractile myofibroblasts in liver cirrhosis. Thus, interactions between ET-1 and Ito cells may have significant