Nitric oxide and cerebral blood flow responses to hyperbaric oxygen

We have tested the hypothesis that cerebral nitric oxide (NO) production is involved in hyperbaric O-2 (HBO2) neurotoxicity. Regional cerebral blood f low (rCBF) and electroencephalogram (EEG) were measured in anesthetized rat s during O-2 exposure to 1, 3, 4, and 5 ATA with or without administration of the NO synthase inhibitor (N-omega-nitro-L-arginine methyl ester), L-arg inine, NO donors, or the N-methyl-D-aspartate receptor inhibitor MK-801. Af ter 30 min of O-2 exposure at 3 and 4 ATA, rCBF decreased by 26-39% and by 37-43%, respectively, and was sustained for 75 min. At 5 ATA, rCBF decrease d over 30 min in the substantia nigra by one-third but, thereafter, gradual ly returned to preexposure levels, preceding the onset of EEG spiking activ ity. Rats pretreated with N-omega-nitro-L-arginine methyl ester and exposed to HBO2 at 5 ATA maintained a low rCBF. MK-801 did not alter the cerebrova scular responses to HBO2 at 5 ATA but prevented the EEG spikes. NO donors i ncreased rCBF in control rats but were ineffective during HBO2 exposures. T he data provide evidence that relative lack of NO activity contributes to d ecreased rCBF under HBO2, but, as exposure time is prolonged, NO production increases and augments rCBF in anticipation of neuronal excitation.