A narrow therapeutical window of a nitric oxide synthase inhibitor against transient ischemic brain injury.
N omega-nitro-L-arginine (0.3-10 mg/kg), a nitric oxide (NO) synthase inhibitor, was administered i.p. to gerbils subjected to 10 min of carotid artery occlusion seven times at 5 min, 3, 6, 24, 48, 72 and 96 h after recirculation. Histopathological examination of the brains obtained 6 days after reflow disclosed that N omega-nitro-L-arginine possesses an ability to mitigate neuronal necrosis in the CA1 subfield of the hippocampus with an optimal dosage of 3 mg/kg. These results strongly suggest that NO synthase activation is at least partly involved in the pathogenetic cellular mechanisms underlying selective neuronal necrosis following cerebral ischemia.
Nagafuji
T
T
CNS Research Division, Fuji-Gotenba Research Laboratories, Chugai Pharmaceutical Co. Ltd., Shizuoka, Japan.
Sugiyama
M
M
Matsui
T
T
Koide
T
T
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005849:Gerbillinae; D006624:Hippocampus / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007274:Injections, Intraperitoneal; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000473:pathology; D019001:Nitric Oxide Synthase; D019335:Nitroarginine
D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases