NITRIC-OXIDE PRODUCTION DURING FOCAL CEREBRAL-ISCHEMIA IN RATS

Background and Purpose: Nitric oxide has been implicated as a mediator of glutamate excitotoxicity in primary neuronal cultures. Methods: A number of indicators of brain nitric oxide production (nitrite and cyc lic guanosine monophosphate [cGMP] concentrations and nitric oxide syn thase activity) were examined after bilateral carotid ligation and rig ht middle cerebral artery occlusion in adult rats. Results: Brain nitr ite was significantly increased in the right versus left cortex 5, 10, and 20 minutes after middle cerebral artery occlusion (P<.05), with a return to baseline at 60 minutes. There were no significant changes i n cerebellar concentrations. Cortical levels of cGMP were increased at 10, 20, and 60 minutes after occlusion, with significant right-to-lef t differences (P<.05). Cerebellar concentrations of cGMP were also inc reased but without significant side-to-side differences. Nitric oxide synthase activity increased approximately 10-fold from baseline 10 min utes after occlusion in the right cortex but decreased markedly by 60 minutes from its peak at 10 minutes. The right-to-left difference in n itric oxide synthase activity was significant at 20 minutes (P<.05). P retreatment of rats with N(G)-nitro-L-arginine, a nitric oxide synthas e inhibitor, abolished the rise in nitrite and cGMP. Conclusions: Thes e results suggest that a sharp transient increase in the activity of n itric oxide synthase occurs during the first hour of cerebral ischemia , which leads to a burst in nitric oxide production and activation of guanylate cyclase.