Endothelin-1 production by hepatic endothelial cells: characterization and augmentation by endotoxin exposure.
Activation of endothelin (ET) receptors in the liver causes vasoconstriction, glucose production, and lipid and peptide mediator synthesis. In the intact rat, a bolus infusion of endotoxin into a mesenteric vein served as an acute exposure model of endotoxemia. In response to this challenge, a ninefold increase in hepatic ET-1 mRNA occurred within 3 h. The plasma level of immunoreactive ET-1 (irET-1) increased correspondingly by 8.5-fold within 6 h. ET-1 mRNA levels in liver endothelial cells (EC) isolated from livers of endotoxin-treated rats at various times after endotoxin challenge showed a more gradual increase. Northern blot analyses of the major liver cell types demonstrated that ET-1 mRNA was most abundant in the EC. The present results document a significant increase in the circulating level of irET-1 during episodes of endotoxemia. The increased hepatic ET-1 production in response to endotoxin 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.
Eakes
A T
AT
Department of Biochemistry, University of Texas Health Science Center at San Antonio, 78284-7760, USA.
Howard
K M
KM
Miller
J E
JE
Olson
M S
MS
D000818:Animals; D019332:Endothelin-1 / Q000096:biosynthesis*; D004727:Endothelium / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D013997:Time Factors
D019332:Endothelin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin