L-nitroarginine, an inhibitor of NO synthase, dramatically worsens limbic epilepsy in rats.
During status epilepticus provoked by an intra-amygdala injection of kainic acid, the severity of seizures and of consequent neuronal damage was considerably increased in rats treated with L-NOARG, at a dose which completely inhibited NO synthesis. We propose that the effects of L-NOARG could be related to the loss of a retrograde inhibition exerted by NO on NMDA receptors. The complete suppression of NO formation in the brain finally facilitated the development and the generalization of seizures and their neurotoxic consequences.
Rondouin
G
G
CNRS UPR9008, INSERM U249, Laboratoire de Médecine Expérimentale, Institut de Biologie, Montpellier, France.
Bockaert
J
J
Lerner-Natoli
M
M
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000679:Amygdala; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D004829:Epilepsy, Generalized / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D007267:Injections; D007608:Kainic Acid; D008032:Limbic System / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology
D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007608:Kainic Acid