title: Inhibition of nitric oxide synthesis aggravates reperfusion injury after hepatic ischemia and endotoxemia.
abstract: The potential role of nitric oxide (NO) was investigated in the pathophysiology of liver injury after priming with 20 min hepatic ischemia-reperfusion and administration of .5 mg/kg Salmonella enteritidis endotoxin. Liver injury during the early reperfusion phase of 4 h was characterized by severe vascular oxidant stress, lipid peroxidation (LPO), neutrophil infiltration, and a 33% reduction of the microvascular blood flow in the liver. Inhibition of NO synthesis with N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME) aggravated liver injury by 90%, reduced LPO, and did not affect liver neutrophils but further impaired microvascular blood flow. Treatment with the NO-donor spermine-NONOate or L-arginine did not affect these parameters in postischemic animals, however, treatment did restore all values of L-NAME-treated animals back to disease control levels. These data suggest that endogenous NO formation is sufficient to limit ischemic liver injury during reperfusion but inhibition of NO synthesis will result in additional ischemic damage. NO may also be involved in scavenging of superoxide in the vasculature and in inducing LPO.
authors.affiliation: Upjohn Company, Kalamazoo, Michigan 49001, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: W R
authors.initials: WR
authors.lastname: Mathews
authors.forename: D M
authors.initials: DM
authors.lastname: Guido
authors.forename: A
authors.initials: A
authors.lastname: Farhood
authors.forename: H
authors.initials: H
authors.lastname: Jaeschke
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000378:metabolism; D005978:Glutathione / Q000097:blood; D007511:Ischemia / Q000150:complications* / Q000503:physiopathology; D015227:Lipid Peroxidation; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000209:etiology* / Q000503:physiopathology; D014115:Toxemia / Q000150:complications* / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D004731:Endotoxins; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000410:Alanine Transaminase; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester