NF-κB induction during in vivo hypoxia in dorsocaudal brain stem of rat: effect of MK-801 andl-NAME

In the nucleus of the solitary tract, NMDA receptors are critical for the hypoxic ventilatory response while neuronal nitric oxide synthase (NOS) modulates the late component of this response. Nuclear factor (NF)-κB is a ubiquitous transcription factor that increases the expression of multiple stress-activated genes. We sought to examine temporal changes in expression of NF-κB within the dorsocaudal brain stem of conscious rats after exposures to 10% O2. Time-dependent increases in NF-κB occurred with hypoxia and peaked at 60 min. Pretreatment with the N-methyl-d-aspartate (NMDA)-receptor channel antagonist dizocilpine maleate (MK-801) markedly attenuated NF-κB complexes during hypoxia. In contrast, after NOS inhibition with N G-nitro-l-arginine methyl ester (l-NAME), although NF-κB was diminished in normoxia, increased NF-κB expression still occurred with hypoxia. Increased phosphorylation of the NF-κB regulatory unit [inhibitory (I)κB] was detected by immunoblotting and also peaked at 60 min. Phosphorylation of Iκ-B during hypoxia was attenuated by MK-801 but not byl-NAME. Thus NMDA-receptor activation in the dorsocaudal brain stem during hypoxia elicits in NF-κB activity marked enhancements that are unaffected after NOS blockade.