Nitric oxide synthase and postischemic liver injury.
The objective of this study was to determine what roles the endothelial cell and inducible isoforms of nitric oxide synthase (eNOS, iNOS) play in ischemia 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%) liver ischemia and 5 h of reperfusion induced substantial liver injury as assessed by the release of large and significant amounts of the liver-specific enzyme alanine aminotransferase (ALT) into the serum of wild-type (wt) mice. The enhanced ALT levels were not due to increased recruitment of potentially damaging PMNs, which could mediate hepatocyte injury, as neither histopathological inspection nor quantitative MPO determinations revealed the presence 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-deficient mice subjected to liver I/R compared to postischemic wt mice. Taken together, these data suggest that eNOS- but not iNOS-derived NO plays an important role in limiting or downregulating I/R-induced liver injury in vivo following 5 h of reperfusion.
Kawachi
S
S
Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, Louisiana, 71130, USA.
Hines
I N
IN
Laroux
F S
FS
Hoffman
J
J
Bharwani
S
S
Gray
L
L
Leffer
D
D
Grisham
M B
MB
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D022781:Hepatocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008099:Liver / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000097:blood / Q000201:enzymology* / Q000276:immunology / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D007527:Isoenzymes; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019001:Nitric Oxide Synthase; D000410:Alanine Transaminase