Effects of 7-nitroindazole and N-nitro-l-arginine methyl ester on changes in cerebral blood flow and nitric oxide production preceding development of hyperbaric oxygen-induced seizures in rats

Hyperbaric oxygen (HBO2) exposure induces increases in cerebral blood flow (CBF) and extracellular concentrations of nitric oxide (NO) that precede the appearance of central nervous system toxicity, which may manifest as convulsions. To elucidate the origins of NO production during HBO2 exposure, we examined the effects of the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole (7-NI), and the non-selective NOS inhibitor, N-nitro-l-arginine methyl ester (l-NAME), on changes in CBF and NO metabolites (NOx, nitrite and nitrate) using a laser Doppler flow probe and in vivo microdialysis techniques, respectively. Rats were anesthetized, artificially ventilated, and pressurized to 5 atmosphere absolute (ATA) with pure oxygen for 60 min. In rats treated with vehicle, CBF and NOx levels in the cortex increased to 201% and 239% of basal levels, respectively, before the onset of electrical discharges, measured by electroencephalogram. The increase in CBF and NOx was completely inhibited by 7-NI and l-NAME. Both drugs also inhibited the appearance of electrical discharges for 60 min. Dynamic changes in CBF and NOx were not significantly different between 7-NI and l-NAME. These findings suggest that neuronal NOS is the main mediator of NO production associated with increase in CBF leading to the appearance of electrical discharge during HBO2 exposure.