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-nitroindazole (7-NI), respectively, and the precursor of NO, glyceryl trinitrate, on soman-induced seizures, lethality, and neuropathology were studied in rats. It was found that pretreatment of rats with L-NAME and 7-NI potentiated the severity of motor convulsions and enhanced lethality produced by soman. On the other hand, glyceryl trinitrate, administered transdermally at doses ranging from 2.5-5 mg/day 1 day before soman, decreased seizure susceptibility and lethality in soman-intoxicated 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 during soman intoxication. These results indicate that neuronal NO may play a prominent role in seizures by acting as an anticonvulsant and neuroprotectant in soman intoxication.
Lallement
G
G
Centre de Recherches du Service de Santé des Armées, Unité de Neurotoxicologie, La Tronche, France.
Shih
T M
TM
Pernot-Marino
I
I
Baubichon
D
D
Foquin
A
A
McDonough
J H
JH
D000818:Animals; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology*; D012999:Soman / Q000494:pharmacology*
D009569:Nitric Oxide; D012999:Soman; D005996:Nitroglycerin; D019331:NG-Nitroarginine Methyl Ester