Tissue specific activation of the endothelin system in severe acute liver failure.
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| 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.
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| Authors | S Heiden, T Pfab, K von Websky, N Vignon-Zellweger, M Godes, K Relle, P Kalk, F Theuring, W Zidek, Berthold Hocher |
| Journal | European journal of medical research (Eur J Med Res) Vol. 13 Issue 7 Pg. 327-9 (Jul 28 2008) ISSN: 0949-2321 [Print] England |
| PMID | 18700189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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