At. Eakes et al., ENDOTHELIN-1 PRODUCTION BY HEPATIC ENDOTHELIAL-CELLS - CHARACTERIZATION AND AUGMENTATION BY ENDOTOXIN EXPOSURE, American journal of physiology: Gastrointestinal and liver physiology, 35(3), 1997, pp. 605-611
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.