Endogenous nitric oxide and exogenous nitric oxide supplementation in hepatic ischemia-reperfusion injury in the rat

Background. Although nitric oxide (NO) is thought to be beneficial in hepat ic ischemia-reperfusion (I/R), the mechanisms for this effect are not well established. Methods. To investigate the effects of endogenous NO and exogenous NO suppl ementation on hepatic I/R injury and their pathogenic mechanisms, serum ALT and hyaluronic acid (endothelial cell damage), and hepatic malondialdehyde and H2O2 (oxidative stress), myeloperoxidase activity (leukocyte accumulat ion), and endothelin (vasoconstrictor peptide opposite to NO) were determin ed at different reperfusion periods in untreated rats and rats receiving L- NAME, L-NAME+L-arginine, and spermine NONOate (exogenous NO donor). Results. After reperfusion every parameter increased in untreated animals. Endogenous NO synthesis inhibition by L-NAME increased hepatocyte and endot helial damage as compared to untreated rats, which was reverted and even im proved by the addition of L-arginine. Spermine NONOate also improved this d amage. However, different mechanisms account for the beneficial effect of e ndogenous and exogenous NO. Oxidative stress decreased by both L-NAME and L -NAME+L-arginine, but remained unmodified by spermine NONOate, Myeloperoxid ase increased by L-NAME and this effect was reverted by the addition of L-a rginine, whereas no change was observed with spermine NONOate, Endothelin l evels were not modified by L-NAME and L-NAME+L-arginine, but decreased with spermine NONOate, Conclusions. These results suggest that, although both endogenous and exoge nous NO exert a protective role in experimental hepatic I/R injury, the mec hanisms of the beneficial effect of the two sources of NO are different.