title: Tissue specific activation of the endothelin system in severe acute liver failure.
abstract: The endothelin system has been implicated in the pathogenesis of acute liver failure. However, it has not yet been assessed in a tissue specific manner. - Acute liver failure was induced in rats by two intraperitoneal injections of galactosamine (1.3 g/kg, interval of 12 hours, n = 20). The animals were sacrificed after 48 hours. - Plasma measurements demonstrated that animals receiving galactosamine had a laboratory constellation of severe liver injury and they histologically presented with hepatic necrosis and inflammation. Plasma concentrations of endothelin-1 were elevated 60-fold in the animals receiving galactosamine (p = 0.005). In contrast endothelin-1 tissue contents were decreased in the kidneys and unchanged in the liver. Western blot analysis showed that animals receiving galactosamine had a significantly lower endothelin B receptor concentration in liver and kidney tissue, whereas no differences were detected for endothelin A receptors. - This study demonstrates that the local endothelin system of liver and kidneys is not responsible for the increase of plasma endothelin-1 concentrations in acute liver failure. Since it is well established that the endothelin B receptor acts as a clearance receptor, its decreased density might contribute to the strongly elevated plasma endothelin-1 concentrations seen in this model of acute liver injury.
authors.affiliation: Center for Cardiovascular Research / Institute of Pharmacology, Charite, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Heiden
authors.forename: T
authors.initials: T
authors.lastname: Pfab
authors.forename: K
authors.initials: K
authors.lastname: von Websky
authors.forename: N
authors.initials: N
authors.lastname: Vignon-Zellweger
authors.forename: M
authors.initials: M
authors.lastname: Godes
authors.forename: K
authors.initials: K
authors.lastname: Relle
authors.forename: P
authors.initials: P
authors.lastname: Kalk
authors.forename: F
authors.initials: F
authors.lastname: Theuring
authors.forename: W
authors.initials: W
authors.lastname: Zidek
authors.forename: Berthold
authors.initials: B
authors.lastname: Hocher
mesh_terms: D000818:Animals; D016232:Endothelins / Q000097:blood / Q000378:metabolism*; D005688:Galactosamine; D007249:Inflammation; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D017093:Liver Failure / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D016232:Endothelins; D005688:Galactosamine