ENDOTHELIN-1 PRODUCTION BY HEPATIC ENDOTHELIAL-CELLS - CHARACTERIZATION AND AUGMENTATION BY ENDOTOXIN EXPOSURE

Activation of endothelin (ET) receptors in the liver causes vasoconstr iction, glucose production, and lipid and peptide mediator synthesis. In the intact rat, a bolus infusion of endotoxin into a mesenteric vei n served as an acute exposure model of endotoxemia. In response to thi s challenge, a ninefold increase in hepatic ET-1 mRNA occurred within 3 h. The plasma level of immunoreactive ET-1 (irET-1) increased corres pondingly by 8.5-fold within 6 h. ET-1 mRNA levels in liver endothelia l cells (EC) isolated from livers of endotoxin-treated rats at various times after endotoxin challenge showed a more gradual increase. North ern blot analyses of the major liver cell types demonstrated that ET-1 mRNA was most abundant in the EC. The present results document a sign ificant increase in the circulating level of irET-1 during episodes of endotoxemia. The increased hepatic ET-1 production in response to end otoxin infusion suggests that ET-1 produced in the liver could make a significant contribution to the plasma irET-1 and may be an important component in the hepatic responses to systemic trauma.