Anticonvulsant and proconvulsant roles of nitric oxide in experimental epilepsy models.
The effect of acute (120 mg/kg) and chronic (25 mg/kg, twice a day, for 4 days) intraperitonial injection of the nitric oxide (NO) synthase (NOS) inhibitor NG-nitro-L-arginine (L-NOARG) was evaluated on seizure induction by drugs such as pilocarpine and pentylenetetrazole (PTZ) and by sound stimulation of audiogenic seizure-resistant (R) and audiogenic seizure-susceptible (S) rats. Seizures were elicited by a subconvulsant dose of pilocarpine (100 mg/kg) only after NOS inhibition. NOS inhibition also simultaneously potentiated the severity of PTZ-induced limbic seizures (60 mg/kg) and protected against PTZ-induced tonic seizures (80 mg/kg). The audiogenic seizure susceptibility of S or R rats did not change after similar treatments. In conclusion, proconvulsant effects of NOS inhibition are suggested to occur in the pilocarpine model and in the limbic components of PTZ-induced seizures, while an anticonvulsant role is suggested for the tonic seizures induced by higher doses of PTZ, revealing inhibitor-specific interactions with convulsant dose and also confirming the hypothesis that the effects of NOS inhibitors vary with the model of seizure.
Del-Bel
E A
EA
Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, SP, Brasil.
Oliveira
P R
PR
Oliveira
J A
JA
Mishra
P K
PK
Jobe
P C
PC
Garcia-Cairasco
N
N
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D000927:Anticonvulsants; D003292:Convulsants; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase