Hyperbaric oxygen reduces cerebral blood flow by inactivating nitric oxide

Based on recent evidence that nitric oxide (NO.) is involved in hyperoxic v asoconstriction, we tested the hypothesis that decreases in NO. availabilit y in brain tissue during hyperbaric oxygen (HBO2) exposure contribute to de creases in regional cerebral blood flow (rCBF). rCBF was measured in rats e xposed to HBO2 at 5 atmospheres (ATA) and correlated with interstitial brai n 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 di smutase (MnSOD) during HBO2. After 30 min of O-2 exposure at 5 ATA, rCBF ha d decreased in the substantia nigra, caudate putamen, hippocampus, and pari etal cortex by 23 to 37%. These reductions in rCBF were not augmented by ex posure to HBO2 in animals pre-treated with L-NAME. After 30 min at 5 ATA, b rain NOx levels had decreased by 31 +/- 9% and correlated with the decrease in rCBF, while estimated (OH)-O-. production increased by 56 +/- 8%. The d ecrease in rCBF at 5 ATA was completely abolished by MnSOD administration i nto the circulation before HBO2 exposure. Doses of NO. donor that significa ntly 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 wi th a decrease in effective NO. concentration and an increase in ROS product ion in the brain. The data support the hypothesis that inactivation of NO. antagonizes basal relaxation of cerebral vessels during HBO2 exposure, alth ough an effect of HBO2 on NO. synthesis has not been excluded. (C) 2000 Aca demic Press.