title: Hyperoxia but not ambient pressure decreases tetrahydrobiopterin level without affecting the enzymatic capability of nitric oxide synthase in human endothelial cells.
abstract: Nitric oxide (NO) seems to be related to bubble formation and endothelial dysfunction resulting in decompression sickness. Bubble formation can be affected by aerobic exercise or manipulating NO. A prior heat stress (HS) has been shown to confer protection against decompression sickness in rats. An important question was if the oxidative environment experienced during diving limits the availability of the nitric oxide synthase (NOS) cofactor tetrahydrobiopterin (BH4). Human endothelial cells were used to investigate how HS and simulated diving affected NO synthesis and defense systems such as heat shock protein 70 (HSP70) and glutathione (GSH). BH4 was measured using a novel LC-MS/MS method and NOS by monitoring the conversion of radiolabeled L-arginine to L-citrulline. Increased pO₂ reduced BH4 levels in cells in a dose-dependent manner independently of high pressure. This effect may result in decreased generation of NO by NOS. The BH4 decrease seemed to be abolished when cells were exposed to HS prior to hyperoxia. NOS enzyme was unaffected by increased pO₂ but substantially reduced after HS. The BH4 level seemed to a minor extent to be dependent upon GSH and probably to a higher degree dependent on other antioxidants such as ascorbic acid. A simulated dive at 60 kPa O₂ had a potentiating effect on the heat-induced HSP70 expression, whereas GSH levels were unaffected by hyperoxic exposure. HS, hyperoxia, and dive affected several biochemical parameters that may play important roles in the mechanisms protecting against the adverse effects of saturation diving.
authors: Norwegian Underwater Intervention AS, 5848, Bergen, Norway. lise.fismen@med.uib.no
authors: Lise
authors: L
authors: Fismen
authors: Torunn
authors: T
authors: Eide
authors: Astrid
authors: A
authors: Hjelde
authors: Asbjørn M
authors: AM
authors: Svardal
authors: Rune
authors: R
authors: Djurhuus
mesh_terms: D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D003664:Decompression; D005978:Glutathione / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D018496:Hyperoxia / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D001708:Biopterins; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C003402:sapropterin; D005978:Glutathione; D010100:Oxygen
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