THE ROLE OF NITRIC-OXIDE IN SOMAN-INDUCED SEIZURES, NEUROPATHOLOGY, AND LETHALITY

The effects of the inhibitors of endothelial and neuronal nitric oxide (NO) synthases, N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroi ndazole (7-NI), respectively, and the precursor of NO, glyceryl trinit rate, on soman-induced seizures, lethality, and neuropathology were st udied in rats. It was found that pretreatment of rats with L-NAME and 7-NI potentiated the severity of motor convulsions and enhanced lethal ity produced by soman. On the other hand, glyceryl trinitrate, adminis tered transdermally at doses ranging from 2.5-5 mg/day 1 day before so man, decreased seizure susceptibility and lethality in soman intoxicat ed animals. This was accompanied by a subsequent reduction of central neuronal damage 24 h after soman treatment. Pretreatment with glyceryl trinitrate also reversed seizure latency produced by 7-NI treatment d uring soman intoxication. These results indicate that neuronal NO may play a prominent role in seizures by acting as an anticonvulsant and n europrotectant in soman intoxication.