Endothelin-1 production by hepatic endothelial cells:
characterization and augmentation by endotoxin exposure.
Eakes, Ann T., Katherine M. Howard, Joseph E. Miller, and Merle S.
Olson.
Department of Biochemistry, University of Texas Health Science
Center at San Antonio, San Antonio, Texas 78284-7760
APStracts 3:0223G, 1996.
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 9-fold increase in hepatic ET-1 mRNA
occurred within 3 hours. The plasma level of immunoreactive ET-1
(irET-1) increased correspondingly by 8.5-fold within 6 hours. ET-1
mRNA levels in liver endothelial cells (EC) isolated from livers of
endotoxin-treated rats at various times following 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.
Received 9 July 1996; accepted in final form 30 September 1996.
APS Manuscript Number G280-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996