title: Stimulation of perivascular nitric oxide synthesis by oxygen.
abstract: We hypothesized that elevated partial pressures of O(2) would increase perivascular nitric oxide (*NO) synthesis. Rodents with O(2)- and.NO-specific microelectrodes implanted adjacent to the abdominal aorta were exposed to O(2) at partial pressures from 0.2 to 2.8 atmospheres absolute (ATA). Exposures to 2.0 and 2.8 ATA O(2) stimulated neuronal (type I) NO synthase (nNOS) and significantly increased steady-state.NO concentration, but the mechanism for enzyme activation differed at each partial pressure. At both pressures, elevations in.NO concentration were inhibited by the nNOS inhibitor 7-nitroindazole and the calcium channel blocker nimodipine. Enzyme activation at 2.0 ATA O(2) appeared to be due to an altered cellular redox state. Exposure to 2.8 ATA O(2), but not 2.0 ATA O(2), increased nNOS activity by enhancing nNOS association with calmodulin, and an inhibitory effect of geldanamycin indicated that the association was facilitated by heat shock protein 90. Infusion of superoxide dismutase inhibited.NO elevation at 2.8 but not 2.0 ATA O(2). Hyperoxia increased the concentration of.NO associated with hemoglobin. These findings highlight the complexity of oxidative stress responses and may help explain some of the dose responses associated with therapeutic applications of hyperbaric oxygen.
authors.affiliation: Department of Emergency Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA. sthom@mail.med.upenn.edu
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Thom
authors.forename: Donald
authors.initials: D
authors.lastname: Fisher
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Veena M
authors.initials: VM
authors.lastname: Bhopale
authors.forename: S Tsuyoshi
authors.initials: ST
authors.lastname: Ohnishi
authors.forename: Yashige
authors.initials: Y
authors.lastname: Kotake
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Donald G
authors.initials: DG
authors.lastname: Buerk
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000737:chemistry / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000032:analysis / Q000378:metabolism; D004567:Electrodes, Implanted; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism; D006931:Hyperbaric Oxygenation; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008839:Microelectrodes; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen / Q000008:administration & dosage*; D010313:Partial Pressure; D010766:Phosphorylation; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000032:analysis
chemical_list: D002121:Calcium Channel Blockers; D002147:Calmodulin; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D007191:Indazoles; D013481:Superoxides; D009569:Nitric Oxide; D009553:Nimodipine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496322:Nos1 protein, rat; C496315:Nos3 protein, mouse; C496316:Nos3 protein, rat; D013482:Superoxide Dismutase; D010100:Oxygen; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester