APStracts 2:0144G, 1995.

Sources of arginine for induced nitric oxide synthesis in the isolated perfused liver. Pastor, Cm, Sm Morris, Jr, and Tr Billiar. Departments of Surgery and Molecular Genetics & Biochemistry, University of Pittsburgh, Pittsburgh, PA 15261

APStracts 2:0144G, 1995.

Hepatocytes can be stimulated to express high levels of inducible nitric oxide synthase (iNOS) which utilizes arginine for NO synthesis. Hepatocytes also synthesize and catabolize arginine, an intermediate in the urea cycle, raising the possibility that the urea pathway may provide substrate for hepatic NO synthesis. To identify the sources of arginine for iNOS, we measured the release of NO2- + NO3- and urea in isolated rat livers perfused in a recirculation model with a Krebs-Henseleit-bicarbonate buffer containing either no added amino acid, arginine, or precursors for urea synthesis. To induce iNOS expression, rats were injected with killed Corynebacterium parvum (C. parvum) or with endotoxin. In livers from C. parvum- and endotoxin-treated rats, we found that : 1. an intracellular source of arginine exists which provides substrate to iNOS; 2. additional exogenous arginine increases NO synthesis, demonstrating that endogenous arginine is insufficient for maximal NO synthesis; 3. an increase in rate of endogenous arginine synthesis within the urea cycle is inefficient in increasing NO synthesis, demonstrating the independence of the two pathways in the liver.

Received 17 October 1994; accepted in final form 23 June 1995.
APS Manuscript Number G418-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.