Nitric oxide synthase and postischemic liver injury

The objective of this study was to determine what roles the endothelial cel l and inducible isoforms of nitric oxide synthase (eNOS, iNOS) play in isch emia and reperfusion (I/R)-induced liver injury in vivo in mice genetically deficient in each isoform of NOS. We found that 45 min of partial (70%) li ver ischemia and 5 h of reperfusion induced substantial liver injury as ass essed by the release of large and significant amounts of the liver-specific enzyme alanine aminotransferase (ALT) into the serum of wild-type (we) mic e. The enhanced ALT levels were not due to increased recruitment of potenti ally damaging PMNs, which could mediate hepatocyte injury, as neither histo pathological inspection nor quantitative MPO determinations revealed the pr esence of PMNs in the liver at this time point. In addition, we observed a significant enhancement in liver injury in eNOS-deficient but not iNOS-defi cient mice subjected to liver I/R compared to postischemic wt mice. Taken t ogether, these data suggest that eNOS- but not iNOS-derived NO plays an imp ortant role in limiting or downregulating VR-induced liver injury in vivo f ollowing 5 h of reperfusion. (C) 2000 Academic Press.