INDUCIBLE NITRIC-OXIDE SYNTHASE FOLLOWING HYPOXIA IN RAT CULTURED GLIAL-CELLS

Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) e xerts inhibitory and cytotoxic effects on various cells including neur onal cells. In the present study, we examined the ability of rat glial cells to produce NO following hypoxia/reoxygenation in vitro by measu ring nitrite. The levels of nitrite produced in the cultured media of glial cells significantly increased after 12-h hypoxia but not after 0 - and 6-h hypoxia. The NOS inhibitor, N-G-monomethyl-L-arginine, decre ased hypoxia-induced nitrite formation. In glial cells after hypoxia/r eoxygenation, the iNOS mRNA and protein expressions were detected by r everse-transcription polymerase chain reaction and by immunocytochemic al analysis, respectively. The present study provides the first eviden ce that hypoxia induces NO production from glial cells. This hypoxia-i nduced, glial cell-derived NO may play a critical role in the pathogen esis of cerebral ischemia in vivo.