Tissue specific activation of the endothelin system in severe acute liver failure

• Published in: European journal of medical research Vol. 13; no. 7; p. 327
• Main Authors: Heiden, S, Pfab, T, von Websky, K, Vignon-Zellweger, N, Godes, M, Relle, K, Kalk, P, Theuring, F, Zidek, W, Hocher, Berthold
• Format: Journal Article
• Language: English
• Published: England 28-07-2008
• Subjects: Animals; Endothelins - blood; Endothelins - metabolism; Galactosamine; Inflammation; Kidney - metabolism; Liver - metabolism; Liver Failure - chemically induced; Liver Failure - diagnosis; Liver Failure - metabolism; Male; Models, Biological; Necrosis; Rats; Rats, Sprague-Dawley; Tissue Distribution
• ISSN: 0949-2321

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.