Nitric oxide production is enhanced in rat brain before oxygen-induced convulsions

Central nervous system oxygen toxicity (CNS O-2 toxicity) is preceded by release of hyperoxic vasoconstriction. which increases regional cerebral blood flow (rCBF). These increases in rCBF precede the onset of O-2-induced convulsions. We have tested the hypothesis that hyperbaric oxygen (HBO2) stimulates NO- production in the brain that leads to hyperemia and anticipates electrical signs of neurotoxicity. We measured rCBF and EEG responses in rats exposed at 4 to 6 atmospheres (ATA) of HBO2 and correlated them with brain interstitial NO- metabolites (NOx) as an index of NO- production. During exposures to hyperbaric oxygen rCBF decreased at 4 ATA, decreased for the initial 30 min at 5 ATA then gradually increased, and increased within 30 min at 6 ATA. Changes in rCBF correlated positively with NOx production: increases in rCBF during HBO2 exposure were associated with large increases in NOx at 5 and 6 ATA and always preceded EEG discharges as a sign of CNS O-2 toxicity. In rats pretreated with L-NAME, rCBF remained maximally decreased throughout 75 min of HBO2 at 4, 5 and 6 ATA. These data provide the first direct evidence that increased NO- production during prolonged HBO2 exposure is responsible for escape from hyperoxic vasoconstriction. The finding suggests that NO- over-production initiates CNS O-2 toxicity by increasing rCBF, which allows excessive O-2 to be delivered to the brain. (C) 2001 Published by Elsevier Science B.V.