Role of nitric oxide system in hydroxyl radical generation in rat striatum due to carbon monoxide poisoning, as determined by microdialysis.
We explored the possible role of the nitric oxide (NO) system in hydroxyl radical (*OH) generation induced by carbon monoxide (CO) poisoning in rat striatum by means of microdialysis with the use of NO synthase (NOS) inhibitors, N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-monomethyl-L-arginine (L-NMMA), as well as L-arginine (L-Arg; the NOS substrate) and D-arginine (D-Arg). The CO-induced *OH generation was suppressed by both L-Arg and D-Arg. It was also suppressed by L-NAME, which inhibits generation of reactive oxygen species (ROS) via neuronal NOS (nNOS) and inducible NOS, but not via endothelial NOS. In contrast, L-NMMA, which inhibits only ROS generation via inducible NOS, potentiated the *OH generation. L-Arg completely reversed the L-NAME effect and partly reversed the L-NMMA effect. D-Arg reversed the L-NAME effect more potently than did L-Arg, resulting in much more *OH generation than was observed with CO alone, and also potentiated the L-NMMA effect. On the other hand, W-7, an antagonist of calmodulin, which is critical for nNOS activity, had no effect on the CO-induced *OH generation. These findings suggest that complex mechanisms operate in *OH generation in rat striatum upon CO poisoning and that the NO system might not be included among those mechanisms.
Hara
Shuichi
S
Department of Forensic Medicine, Tokyo Medical University, 6-1-1 Shinjuku, Tokyo, Japan. s-hara@tokyo-med.ac.jp
Mukai
Toshiji
T
Kurosaki
Kunihiko
K
Mizukami
Hajime
H
Kuriiwa
Fumi
F
Endo
Takahiko
T
D000280:Administration, Inhalation; D000818:Animals; D000963:Antimetabolites / Q000633:toxicity*; D001120:Arginine / Q000494:pharmacology; D002248:Carbon Monoxide / Q000633:toxicity*; D002249:Carbon Monoxide Poisoning / Q000378:metabolism*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D019570:Inhalation Exposure; D008297:Male; D017551:Microdialysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000963:Antimetabolites; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D002248:Carbon Monoxide; D001120:Arginine; D052248:Nitric Oxide Synthase Type I; D019331:NG-Nitroarginine Methyl Ester