title: Effects of hyperbaric oxygen on nitric oxide generation in humans.
abstract: BACKGROUND
  Hyperbaric oxygen (HBO2) has been suggested to affect nitric oxide (NO) generation in humans. Specific NO synthases (NOSs) use L-arginine and molecular oxygen to produce NO but this signaling radical may also be formed by serial reduction of the inorganic anions nitrate and nitrite. Interestingly, commensal facultative anaerobic bacteria in the oral cavity are necessary for the first step to reduce nitrate to nitrite. The nitrate-nitrite-NO pathway is greatly potentiated by hypoxia and low pH in contrast to classical NOS-dependent NO generation. We investigated the effects of HBO2 on NO generation in healthy subjects including orally and nasally exhaled NO, plasma and salivary nitrate and nitrite as well as plasma cGMP and plasma citrulline/arginine ratio. In addition, we also conducted in-vitro experiments in order to investigate the effects of hyperoxia on nitrate/nitrite metabolism and NO generation by oral bacteria.
  
  
  METHODS
  Two separate HBO2 experiments were performed. In a cross-over experiment (EXP1) subjects breathed air at 130 kPa (control) or oxygen at 250 kPa for 100 minutes and parameters were measured before and after exposure. In experiment 2 (EXP 2) measurements were performed also during HBO2 at 250 kPa for 110 minutes.
  
  
  RESULTS
  HBO2 acutely reduced orally and nasally exhaled NO by 30% and 16%, respectively. There was a marked decrease in salivary nitrite/nitrate ratio during and after HBO2, indicating a reduced bacterial conversion of nitrate to nitrite and NO. This was supported by in vitro experiments with oral bacteria showing that hyperoxia inhibited bacterial nitrate and nitrite reduction leading to reduced NO generation. Plasma nitrate was unaffected by HBO2 while plasma nitrite was reduced during HBO2 treatment. In contrast, plasma cGMP increased during HBO2 as did citrulline/arginine ratio after treatment and control.
  
  
  CONCLUSIONS
  HBO2-exposure in humans affects NO generation in the airways and systemically differently. These data suggest that the individual NOSs as well as the nitrate-nitrite-NO pathway do not respond in a similar way to HBO2.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Deparment of Anesthesia & Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Uusijärvi
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Deparment of Anesthesia & Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Eriksson
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Agneta C
authors.initials: AC
authors.lastname: Larsson
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Nihlén
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Schiffer
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Lindholm
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Deparment of Anesthesia & Intensive Care, Karolinska University Hospital, Stockholm, Sweden. Electronic address: eddie.weitzberg@ki.se.
authors.forename: Eddie
authors.initials: E
authors.lastname: Weitzberg
mesh_terms: D000328:Adult; D001120:Arginine / Q000097:blood; D001944:Breath Tests; D002956:Citrulline / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D006801:Humans; D006931:Hyperbaric Oxygenation; D009566:Nitrates / Q000032:analysis / Q000097:blood / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D009573:Nitrites / Q000032:analysis / Q000097:blood / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D012463:Saliva / Q000737:chemistry; D014059:Tongue / Q000187:drug effects / Q000382:microbiology; D055815:Young Adult
chemical_list: D009566:Nitrates; D009573:Nitrites; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP; D010100:Oxygen
keywords: Bacteria; Exhaled; Nitrate; Nitrite