Nitric oxide and inducible nitric oxide synthase expression are downregulated in acute cholestasis in the rat accompanied by liver ischemia

Hepatic blood flow decreases under cholestasis and there is evidence that N O regulates liver microvascular perfusion. Thus, the aim of the present stu dy was to evaluate NO synthesis in cholestasis. Cholestasis was induced by bile-duct ligation (BDL) in male Wistar rats. Bilirubins and enzyme activit ies were measured in serum. Lipid peroxidation, GSH, GSSG and glycogen were determined in liver. Histopathological analysis was performed. Serum NO2- + NO3- concentration was measured by the Gries reaction, iNOS immunoblot an alysis was carried out using an iNOS polyclonal antibody. After 7 days of B DL lipid peroxidation increased while GSH/GSSG ratio decreased. Serum NO2- + NO3- and liver iNOS protein were reduced, accompanied by ischemia as reve aled by the histopathological analysis. GSH upregulates NO synthesis by inc reasing iNOS mRNA levels and iNOS activity, thus the reduction of GSH/GSSG ratio may be responsible for the downregulation of iNOS protein and NO synt hesis, which in turn may explain the observed ischemia and the decreased he patic blood perfusion in cholestasis reported by others. (C) 2000 Elsevier Science Inc. All rights reserved.