Effect of NO synthase inhibition on NMDA- and ischaemia-induced hippocampal lesions.
We assessed the effect of NG-Nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, on the hippocampal lesions induced either by the focal injection of N-methyl-D-aspartate (NMDA) or (s)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (s-AMPA) or by 10 min of severe forebrain ischaemia (4-vessel occlusion), in the rat. We find that L-NAME, 20 or 40 mg kg-1, selectively decreases NMDA-induced CA1 lesions while it has no effect on AMPA toxicity. L-NAME, 20 mg kg-1, does not decrease hippocampal damage induced by ischaemia. These results suggest that NO contributes to NMDA toxicity and support data indicating that NMDA receptor antagonists fail to protect against hippocampal CA1 lesions in the 4-vessel occlusion model.
Moncada
C
C
Department of Neurology, Institute of Psychiatry, London, UK.
Lekieffre
D
D
Arvin
B
B
Meldrum
B
B
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002545:Brain Ischemia / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity*; D019331:NG-Nitroarginine Methyl Ester; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity*; D019001:Nitric Oxide Synthase; D011712:Pyramidal Tracts / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D009498:Neurotoxins; D007051:Ibotenic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester