CNS
oxygen (O2) toxicity is complex, and the etiology of its most severe manifestation, O2 convulsions, is yet to be determined. A role for depletion of the brain
GABA pool has been proposed, although recent data have implicated production of reactive O2 species, e.g. H2O2, in this process. We hypothesized that the production of H2O2 and NH3 produced by
monoamine oxidase (
MAO) would lead to depletion of
GABA and production of
nitric oxide (NO.) respectively, and thereby enhance CNS O2 toxicity. In this study, rats treated with an
MAO inhibitor (
pargyline) or a
nitric oxide synthase inhibitor (LNNA) were protected against O2-induced convulsions. Selected cerebral
amino acids including
arginine were measured in control and O2 treated rats (6 ATA, 20 min) with or without
drug pretreatment. After O2 exposure, the cerebral pools of
glutamate,
aspartate, and
GABA decreased significantly while
glutamine content increased relative to control (P < 0.05).
After treatment with either
enzyme inhibitor,
glutamine,
glutamate and
aspartate concentrations were maintained near control levels. Remarkably,
GABA depletion by O2 was not prevented despite protection from
seizures by both
pargyline and LNNA. The NO. precursor,
arginine, was increased significantly in the brain by toxic O2 exposure, but both
pargyline and LNNA inhibited this effect. Simultaneous
norepinephrine measurements indicated that its storage substantially decreased during
hyperoxia (P < 0.05), but this effect too was blocked by either
pargyline or LNNA. These data indicate that protection against O2 by these inhibitors is not related to preservation of the
GABA pool. More importantly, O2 dependent
norepinephrine metabolism and NO. synthesis appear to be interactive during CNS O2 toxicity.