Role of nitric oxide in liver ischemia and reperfusion injury.
The present study was designed to assess the role of endothelial cell and inducible nitric oxide synthase (eNOS, iNOS)-derived NO in ischemia/reperfusion (I/R)-induced pro-inflammatory cytokine expression and tissue injury in a murine model of hepatic I/R. Forty-five min of partial hepatic ischemia and 3 h of reperfusion resulted in a significant increase in liver injury as assessed by serum alanine aminotransferase and histopathology which occurred in the absence of neutrophil infiltration. Both iNOS and eNOS deficient mice exhibited enhanced liver injury when compared to their wild type (wt) controls again in the absence of neutrophil infiltration. Interestingly, message expression for both tumor necrosis factor-alpha (TNF-alpha) and interleukin 12 (IL-12) were enhanced in eNOS, but not iNOS-deficient mice at 1 h post-ischemia when compared to their wt controls. In addition, eNOS message expression appeared to be up-regulated between 1 and 3 h ofreperfusion in wt mice while iNOS deficient mice exhibited substantial increases at I but not 3 h. Taken together, these data demonstrate the ability of eNOS and iNOS to protect the post-ischemic liver, however their mechanisms of action may be very different.
Hines
Ian N
IN
Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, LA 71130, USA.
Kawachi
Shigeyuki
S
Harada
Hirohisa
H
Pavlick
Kevin P
KP
Hoffman
Jason M
JM
Bharwani
Sulaiman
S
Wolf
Robert E
RE
Grisham
Matthew B
MB
D000818:Animals; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase