BIPHASIC ENHANCEMENT OF NITRIC-OXIDE SYNTHASE ACTIVITY AND CGMP LEVELFOLLOWING BRAIN ISCHEMIA IN GERBILS

This study was aimed to examine properties and changes in nitric oxide synthase (NOS) activity and cGMP level during reperfusion after 5 min of brain ischemia in gerbils. Animals were treated 5 min before ische mia with NOS inhibitors: N-Nitro-L-arginine (NNLA), or 7-Nitroindazole (7-NI), or with the inhibitor of guanylate cyclase, LY 83583, or with hydrocortisone for 7 days before ischemia. Northern blot analysis was performed using specific cDNA for inducible NOS. It was observed that ischemia significantly enhances NOS activity and cGMP level. During r eperfusion, biphasic increase in NOS activity and cGMP level took plac e with two peaks 15 min and 2 h after ischemia. NNLA, 7-NI, and LY 835 83 eliminated enhancements of NOS activity and cGMP level, whereas glu cocorticoid remained without effect. There was no activation of gene e ncoding inducible NOS (iNOS). Our results indicate that ischemia-reper fusion activates constitutive NOS. It is suggested that nitric oxide ( NO) production during reperfusion is related to neuronal degeneration and that inhibitor of NOS offers a new therapeutical strategies.