GENE-EXPRESSION OF ENDOTHELIN-1 AND ETA AND ETB RECEPTORS IN HUMAN CIRRHOSIS - RELATIONSHIP WITH HEPATIC HEMODYNAMICS

Previous experimental studies have suggested that the paracrine endoth elin system may participate in the regulation of hepatic hemodynamics in cirrhosis. The present study assesses the relationship between incr eased portal pressure and preproET-1, ETA receptor and ETB receptor ge ne expression in human cirrhosis. PreproET-1, ETA receptor and ETB rec eptor mRNA abundance was estimated by quantitative PCR in human hepati c tissue from subjects with normal liver and in cirrhotic patients in whom a hepatic hemodynamic study was performed. The expression of the three transcripts was significantly higher in liver samples of cirrhot ic patients than in those obtained from subjects without any histologi cal alteration. Moreover, while no significant correlation was found b etween preproET-1 mRNA abundance and portal pressure, there was a high ly significant direct relationship between ETA and ETB receptor gene e xpression and portal pressure in cirrhotic patients. These results ind icate that the liver paracrine endothelin system is overactivated in h uman cirrhosis and that a direct relationship exists between endotheli n receptor mRNA abundance and the degree of portal hypertension in the se patients.