Long-term L-NAME treatment potentiates the blood-brain barrier disruption during pentylenetetrazole-induced seizures in rats.
We investigated whether the severity of blood-brain barrier disruption caused by pentylenetetrazole-induced seizures is modified by long-term nitric oxide synthase inhibition in rats. Rats were given N-omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, in drinking water for 4 weeks, and then treated with pentylenetetrazole to induce seizures. Damage to the blood-brain barrier was investigated using Evans blue dye extravasation. Serum nitric oxide concentration was decreased in L-NAME-treated rats (P<0.01). L-NAME and/or pentylenetetrazole treatments elevated systolic blood pressure of animals (P<0.01). L-NAME caused an increase in the mortality rate after pentylenetetrazole injection leading to the death of animals at about 15 min after the onset of the seizure. Pentylenetetrazole-induced seizures in rats treated with L-NAME caused a significant increase in Evans blue dye extravasation into cerebral cortex, diencephalon and cerebellum, as compared with seizures evoked by pentylenetetrazole injection to L-NAME-untreated rats (P<0.01). Data presented here suggest that the degree of blood-brain barrier disruption induced by seizures is more pronounced in long-term nitric oxide deficiency.
Kalayci
Rivaze
R
Research Institute for Experimental Medicine, Istanbul University, Capa 34390, Istanbul, Turkey.
Kaya
Mehmet
M
Ahishali
Bulent
B
Arican
Nadir
N
Elmas
Imdat
I
Kucuk
Mutlu
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D003292:Convulsants / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005070:Evans Blue; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010433:Pentylenetetrazole / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism*
D003292:Convulsants; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D005070:Evans Blue; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole