title: Nitric oxide synthase-independent generation of nitric oxide in rat skeletal muscle ischemia-reperfusion injury.
abstract: We have used electron paramagnetic resonance to investigate the time course of nitric oxide (NO) generation and its susceptibility to inhibitors of nitric oxide synthase (NOS) in ischemia-reperfusion (IR) injury to rat skeletal muscle in vivo. Significant levels of muscle nitroso-heme complexes were detected 24 h postreperfusion, but not after at 0.05, 3, and 8 h of reperfusion. The levels of muscle nitroso-heme complexes were not decreased by the NOS inhibitor N-nitro-L-arginine methyl ester as a single dose (30 mg/kg) prior to reperfusion or as multiple doses continued throughout the reperfusion (total administered, 120 mg/kg) or by the potent NOS inhibitor S-methylisothiourea (3 mg/kg). In contrast, nitroso-heme levels were reduced by the glucocorticoid dexamethasone (2.5 mg/kg). Muscle necrosis in vitro did not result in the formation of nitroso-heme complexes. The finding that reperfusion after ischemia is necessary for NO formation suggests that an inflammatory pathway is responsible for NOS-independent NO formation in IR injury to skeletal muscle.
authors.affiliation: Bernard O'Brien Institute of Microsurgery, St. Vincent's Hospital, Melbourne, Australia. dianaal@eduserv.its.unimelb.edu.au
authors.forename: D A
authors.initials: DA
authors.lastname: Lepore
authors.forename: A V
authors.initials: AV
authors.lastname: Kozlov
authors.forename: A G
authors.initials: AG
authors.lastname: Stewart
authors.forename: J V
authors.initials: JV
authors.lastname: Hurley
authors.forename: W A
authors.initials: WA
authors.lastname: Morrison
authors.forename: A
authors.initials: A
authors.lastname: Tomasi
mesh_terms: D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D006418:Heme / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D006454:Hemoglobins; D009569:Nitric Oxide; D006418:Heme; D019001:Nitric Oxide Synthase