Effects of hyperbaric oxygen on nitric oxide generation in humans

• Hyperbaric oxygen (HBO2) reduces nasally and orally exhaled NO in humans.
• Nitrate and nitrite reduction to NO by oral bacteria is disrupted by hyperbaric oxygen.
• The decrease in orally exhaled NO by HBO2 partly depends on reduced oral NO generation.
• The decrease in nasally exhaled NO by HBO2 suggests reduced iNOS activity in the nasal airways.
• HBO2 affects NO generation both from NOS-dependent and nitrate/nitrite-dependent pathways.

BackgroundHyperbaric 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.MethodsTwo 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.ResultsHBO2 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.ConclusionHBO2-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.