Different roles of neuronal and endothelial nitric oxide synthases on ischemic nitric oxide production in gerbil striatum

The production of nitric oxide (NO) in gerbil striatum during ischemia and reperfusion was monitored by measuring total NO metabolites in dialysates, and the effects of 7-nitroindazole (7-NI), a selective inhibitor of neurona l NO synthase, and NG-nitro-L-arginine methyl ester (L-NAME), a non-selecti ve inhibitor of NO synthase, were examined. The effects of these agents on ischemic neuronal damage were histo logically evaluated 7 days after transi ent ischemia for 5 or 10 min. 7-NI and L-NAME decreased the NO production t o similar extents in non-ischemic gerbils. 7-NI inhibited the increased NO production after 5 min of ischemia, and partly attenuated the increase in N O production after 10 min of ischemia, but had no effect on the increase af ter 15 min of ischemia. L-NAME completely abolished the increased NO produc tion after different durations of ischemia. The extent of ischemic neuronal damage by 5-min ischemia was aggravated by either 7-NI or L-NAME, while da mage by 10-min ischemia was marked in all groups. These results indicate th at neuronal and endothelial NO synthases make different contributions to th e post-ischemic NO production and the histological outcomes in gerbil stria tum. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.