Nitric oxide and soman poisoning.
OBJECTIVE
To examine whether nitric-oxide (NO) is involved in the toxicity of soman.


METHODS
With pretreatments of icv L-arginine (Arg, the substrate of nitric-oxide synthase NOS), NG-nitro-L-arginine methyl ester (NAME, the inhibitor of NOS), the latency of seizure, and the mortality of mice induced by soman poisoning were examined. The activities of brain NOS in soman-intoxicated mice were measured.


RESULTS
In case of Arg pretreatments, the latency decreased (P < 0.05) from (5.2 +/- 1.8) min (control) to (4.3 +/- 0.8) min (Arg 160 nmol), and the mortality increased (P < 0.05) from 50% (control) to 81% (Arg 160 nmol). In case of NAME pretreatment, the latency increased (P < 0.01) from (4.0 +/- 1.1) min (control) to (14.5 +/- 5.0) min (NAME 2.20 mumol), and the mortality decreased (P < 0.05) from 87% (control) to 50% (NAME 2.20 mumol). The toxicity of soman in mice was enhanced by Arg and reduced by NAME all in a dose-dependent fashion. NAME antagonized the enhancement of soman poisoning by Arg. Intoxication of mice with soman increased the NOS activity in cerebrum, cerebellum, and hippocampus from 100% to 104% (P < 0.05), 115% (P < 0.01), and 111% (P < 0.01), respectively.


CONCLUSIONS
The onset of seizure and death of mice induced by soman poisoning are related to the NO messenger system.
Wang
Y X
YX
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
Sun
M J
MJ
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001921:Brain / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D012640:Seizures / Q000139:chemically induced / Q000201:enzymology; D012999:Soman / Q000506:poisoning*
D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D001120:Arginine; D012999:Soman; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D019331:NG-Nitroarginine Methyl Ester