L-ARGININE-NO PATHWAY AND CNS OXYGEN-TOXICITY

The involvement of the L-arginine-nitric oxide (NO) pathway in the pat hogenesis of hyperoxia-induced seizures was studied by using agents co ntrolling NO levels. We selected two inhibitors of nitric oxide syntha se, the systemic inhibitor N-omega-nitro-L-arginine methyl ester (L-NA ME) and the novel cerebral-specific inhibitor 7-nitroindazole, and two generators of NO, the NO donor S-nitroso-N-acetylpenicillamine and th e physiological precursor L-arginine. Rats with chronic cortical elect rodes were injected intraperitoneally with different doses of one of t he agents or their vehicles before exposure to 0.5 MPa O-2 and O-2 wit h 5% CO2 at an absolute pressure of 0.5 MPa. The duration of the laten t period until the onset of electrical discharges in the electroenceph alogram was used as an index of central nervous system O-2 toxicity. T he two nitric oxide synthase inhibitors L-NAME and 7-nitroindazole sig nificantly prolonged the latent period to the onset of seizures on exp osure to both hyperbaric O-2 and to the hypercapnic-hyperoxic mixture. Pretreatment with the NO donor S-nitroso-N-acetylpenicillamine signif icantly shortened the latent period, whereas L-arginine, the physiolog ical precursor of NO, significantly prolonged the latent period to ons et of seizures. Our results suggest that the L-arginine-NO pathway is involved in the pathophysiology of hyperoxia-induced seizures via vari ous regulating mechanisms.