The roles of iNOS in liver ischemia-reperfusion injury

To determine the contribution of the inducible nitric oxide synthase (iNOS) to hepatic injury following warm ischemia-reperfusion, we developed a mode l of partial hepatic ischernia-reperfusion in mice and studied the injury r esponse in iNOS knockout (KO) mice. Compared with wild types, iNOS KO anima ls exhibited lower plasma transaminase levels after 1 and 6 h of reperfusio n following 1 h of ischemia. At the 3-h time point, enzyme levels were not different between the two groups. iNOS mRNA was not detectable in the ische mic hepatic lobes of wild-type mice until 3 h of reperfusion however, perfu sion studies identified a significant delay in reperfusion of the ischemic lobe In the iNOS KO mice at the 1-h time point with similar perfusion rates at 3 and 6 h compared with wild type. By way of comparison, mice deficient in the endothelial NOS (eNOS) were also assessed for the degree of hepatic damage 3 h post-reperfusion. Plasma transaminase levels were significantly increased in eNOS KO animals compared with wild-type controls. These data suggest that systemic as well as local sources of iNOS regulate reperfusion , and local iNOS contributes to hepatic Injury, while eNOS is protective In warm hepatic ischernia-reperfusion.