Hyperbaric oxygen reduces cerebral blood flow by inactivating nitric oxide

Based on recent evidence that nitric oxide (NO.) is involved in hyperoxic vasoconstriction, we tested the hypothesis that decreases in NO. availability in brain tissue during hyperbaric oxygen (HBO2) exposure contribute to decreases in regional cerebral blood flow (rCBF). rCBF was measured in rats exposed to HBO2 at 5 atmospheres (ATA) and correlated with interstitial brain levels of NO. metabolites (NOx) and production of hydroxyl radical ((OH)-O-.). Changes in rCBF were also correlated with the effects of NO. synthase inhibitor (L-NAME), NO. donor PAPANONOate, and intravascular superoxide dismutase (MnSOD) during HBO2. After 30 min of O-2 exposure at 5 ATA, rCBF had decreased in the substantia nigra, caudate putamen, hippocampus, and parietal cortex by 23 to 37%. These reductions in rCBF were not augmented by exposure to HBO2 in animals pre-treated with L-NAME. After 30 min at 5 ATA, brain NOx levels had decreased by 31 +/- 9% and correlated with the decrease in rCBF, while estimated (OH)-O-. production increased by 56 +/- 8%. The decrease in rCBF at 5 ATA was completely abolished by MnSOD administration into the circulation before HBO2 exposure. Doses of NO. donor that significantly increased rCBF in animals breathing air had no effect at 5 ATA of HBO2. These results indicate that decreases in rCBF with HBO2 are associated with a decrease in effective NO. concentration and an increase in ROS production in the brain. The data support the hypothesis that inactivation of NO. antagonizes basal relaxation of cerebral vessels during HBO2 exposure, although an effect of HBO2 on NO. synthesis has not been excluded. (C) 2000 Academic Press.