Role of nitric oxide in the oxidant stress during ischemia/reperfusion injury of the liver.
The potential role of nitric oxide (NO) and its reaction product with superoxide, peroxynitrite, was investigated in a model of hepatic ischemia-reperfusion injury in male Fischer rats in vivo. Pretreatment with the NO synthase inhibitor nitro-L-arginine (10 mg/kg) did neither affect the post-ischemic oxidant stress and liver injury during the initial reperfusion phase nor the subsequent infiltration of neutrophils into the liver and the later, neutrophil-induced injury phase. Furthermore, no evidence was found for a postischemic increase of the urinary excretion of nitrite, a stable oxidation metabolite of NO. In contrast, the administration of Salmonella enteritidis endotoxin (1 mg/kg) induced a significant diuresis in Fischer rats and an 800-fold enhancement of the urinary nitrite excretion. Nitro-L-arginine pretreatment inhibited the endotoxin-induced nitrite formation by 97%. Hepatic cGMP levels, as index of NO formation in the liver, were only increased significantly after endotoxin administration but not after ischemia and reperfusion. Our results provide no evidence for any enhanced generation of NO or peroxynitrite either systemically or locally during reperfusion and therefore it is unlikely that any of these metabolites are involved in the oxidant stress and liver injury during reperfusion after hepatic ischemia.
Jaeschke
H
H
Department of Medicine, Baylor College of Medicine, Houston, Texas.
Schini
V B
VB
Farhood
A
A
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000652:urine; D019335:Nitroarginine; D016877:Oxidants / Q000009:adverse effects*; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000652:urine; D013312:Stress, Physiological / Q000139:chemically induced*; D013481:Superoxides / Q000378:metabolism
D009566:Nitrates; D009573:Nitrites; D016877:Oxidants; D013481:Superoxides; D019335:Nitroarginine; C039642:peroxynitric acid; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases