Inducible nitric oxide synthase following hypoxia in rat cultured glial cells

Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) exerts inhibitory and cytotoxic effects on various cells including neuronal cells. In the present study, we examined the ability of rat glial cells to produce NO following hypoxia/reoxygenation in vitro by measuring 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, decreased hypoxia-induced nitrite formation. In glial cells after hypoxia/reoxygenation, the iNOS mRNA and protein expressions were detected by reverse-transcription polymerase chain reaction and by immunocytochemical analysis, respectively. The present study provides the first evidence that hypoxia induces NO production from glial cells. This hypoxia-induced, glial cell-derived NO may play a critical role in the pathogenesis of cerebral ischemia in vivo.