title: Role of nitric oxide system in hydroxyl radical generation in rat striatum due to carbon monoxide poisoning, as determined by microdialysis.
abstract: 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.
authors: Department of Forensic Medicine, Tokyo Medical University, 6-1-1 Shinjuku, Tokyo, Japan. s-hara@tokyo-med.ac.jp
authors: Shuichi
authors: S
authors: Hara
authors: Toshiji
authors: T
authors: Mukai
authors: Kunihiko
authors: K
authors: Kurosaki
authors: Hajime
authors: H
authors: Mizukami
authors: Fumi
authors: F
authors: Kuriiwa
authors: Takahiko
authors: T
authors: Endo
mesh_terms: 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
chemical_list: 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