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 co ncomitant with seizures induced by kainate is mainly due to the potent vasodilator nitric oxide (NO). However, the production site of NO act ing at cerebral vessels was undetermined. In the present study, we inv estigated whether NO responsible for the cerebral vasodilation is of e ither neuronal or endothelial origin. We used a putative selective inh ibitor of neuronal NO synthase, 7-nitro indazole (7-NI). CBF was measu red continuously in parietal cortex by means of laser Doppler flowmetr y in awake rats. Systemic variables and electroencephalograms were mon itored. Kainate (10 mg/kg i.p.) was given to rats previously treated w ith saline (n = 8) or 7-NI (25 mg/kg i.p., n = 8) or L-arginine (300 m g/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 mea n arterial blood pressure. Under kainate, 7-NI prevented significant i ncreases in CBF throughout the seizures despite sustained paroxysmal e lectrical activity. L-arginine, the substrate in the production of NO, prevented any decrease in CBF under 7-NI in basal conditions and part ially, 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 pres ent results show that neurons are the source of NO responsible for the cerebrovascular response to seizure activity after kainate systemic i njection.