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B induction during in vivo hypoxia in dorsocaudal brain stem
of rat: effect of MK-801 and
L-NAME
Constance S. Kaufman Pediatric Pulmonary Research Laboratory, Departments of Pediatrics and Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112
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)-
B
is a ubiquitous transcription factor that increases the expression of
multiple stress-activated genes. We sought to examine temporal changes
in expression of NF-
B within the dorsocaudal brain stem of conscious
rats after exposures to 10% O2.
Time-dependent increases in NF-
B 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-
B complexes during hypoxia. In contrast, after NOS inhibition with
NG-nitro-L-arginine methyl
ester (L-NAME),
although NF-
B was diminished in normoxia, increased NF-
B
expression still occurred with hypoxia. Increased phosphorylation of
the NF-
B regulatory unit [inhibitory (I)
B] was
detected by immunoblotting and also peaked at 60 min. Phosphorylation
of I
-B during hypoxia was attenuated by MK-801 but not by
L-NAME. Thus NMDA-receptor
activation in the dorsocaudal brain stem during hypoxia elicits in
NF-
B activity marked enhancements that are unaffected after NOS
blockade.
nuclear factor-
B; NG-nitro-L-arginine methyl ester; hypoxia; transcription factors; nitric oxide; glutamate; N-methyl-D-aspartate
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