DIFFERENTIAL ACTION OF 7-NITRO INDAZOLE ON RAT-BRAIN NITRIC-OXIDE SYNTHASE

We examined the dose-response characteristics of brain nitric oxide sy nthase (NOS) inhibition following intraperitoneal administration of 7- nitro indazole (7-NI). 7-NI inhibited striatal, hippocampal, cortical, cerebellar and nigral NOS activity in a dose-dependent manner. NOS ac tivity in the striatum and hippocampus could not be inhibited more tha n 60% while cerebellar and nigral activity was depleted by at least 85 %, indicating that 7-NI has differential effects in different brain re gions. ED(50) values obtained from the 7-NI dose-response curves of th e striatum and hippocampus were significantly higher than the ED(50) V alues obtained from the cortex, cerebellum and substantia nigra, furth er confirming the differential actions of 7-NI. In addition, inhibitio n of NOS activity 4.5 h following a maximal dose of 7-NI demonstrated differential recovery. At this time point, the cerebellum and hippocam pus were more inhibited than the striatum, cortex and substantia nigra . Therefore, the extent of recovery from this inhibition was independe nt of the level of maximal NOS inhibition in the different brain regio ns. We suggest determining the extent and duration of NOS inhibition r esulting from 7-NI administration prior to using it to study the role of neuronal nitric oxide (NO) in various systems.