Nitric oxide of neuronal origin is involved in cerebral blood flow increase during seizures induced by kainate.
In a previous study, we reported that the sustained increase in CBF concomitant with seizures induced by kainate is mainly due to the potent vasodilator nitric oxide (NO). However, the production site of NO acting at cerebral vessels was undetermined. In the present study, we investigated whether NO responsible for the cerebral vasodilation is of either neuronal or endothelial origin. We used a putative selective inhibitor of neuronal NO synthase, 7-nitro indazole (7-NI). CBF was measured continuously in parietal cortex by means of laser Doppler flowmetry in awake rats. Systemic variables and electroencephalograms were monitored. Kainate (10 mg/kg i.p.) was given to rats previously treated with saline (n = 8) or 7-NI (25 mg/kg i.p., n = 8) or L-arginine (300 mg/kg i.p., n = 8) followed 30 min later by 7-NI (25 mg/kg i.p.). Under basal conditions, 7-NI decreased CBF by 27% without modifying the mean arterial blood pressure. Under kainate, 7-NI prevented significant increases in CBF throughout the seizures despite sustained paroxysmal electrical activity. L-arginine, the substrate in the production of NO, prevented any decrease in CBF under 7-NI in basal conditions and partially, but nonsignificantly, reversed the cerebrovascular influence of 7-NI during seizures. In a separate group of rats (n = 6), inhibition of cortical NO synthase activity by 7-NI was assayed at 73%. The present results show that neurons are the source of NO responsible for the cerebrovascular response to seizure activity after kainate systemic injection.
Montécot
C
C
Laboratoire de Recherches Cérébrovasculaires, CNRS URA 641, IFR 6, University of Paris 7, France.
Borredon
J
J
Seylaz
J
J
Pinard
E
E
D000818:Animals; D002560:Cerebrovascular Circulation; D007608:Kainic Acid; D008297:Male; D009474:Neurons / Q000737:chemistry*; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010296:Parietal Lobe / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology*
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D007608:Kainic Acid