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Constance S. Kaufman Pediatric Pulmonary Research Laboratory, Departments of Pediatrics and Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112
Nitric oxide
(NO) is an excitatory neurotransmitter in the hypoxic ventilatory
response (HVR). Furthermore, neuronal NO synthase (nNOS) activity in
the developing rat correlates with the magnitude of late hypoxic
ventilatory depression. To test the hypothesis that repeated short
exposures to hypoxia may modify late HVR characteristics in young rats,
we conducted 30-min hypoxic challenges in 2- to 3-day-old rat pups,
before (Pre) and 6 h after (Post) they completed a series of eight
cycles consisting of 5 min of hypoxia and 10 min of normoxia (Hyp-Norm)
or normoxia throughout (Norm-Norm). In an additional group, similar
challenges were performed after administration of either
intraperitoneal vehicle or 25 mg/kg 7-nitroindazole (7-NI). Ventilation
(
E) was measured using whole body
plethysmography. Although no changes in peak
E responses occurred with
episodic hypoxia (Pre vs. Post,
P = not significant), late
E reductions were markedly attenuated
in Post (
E from early to late: 7.2 ± 1.5 ml/min in Pre vs. 4.5 ± 1.1 ml/min in Post;
P < 0.002). Furthermore, 7-NI
treatment of Post animals was associated with late
E reductions to Pre levels in
Hyp-Norm-exposed animals. Western blots of protein equivalents from the
caudal brain stem revealed increased nNOS expression in Hyp-Norm
compared with Norm-Norm (P < 0.01).
Current findings suggest that repeated short hypoxic exposures improve
the ability to sustain E, which appears
to be mediated by increased nNOS expression and activity in brain stem
respiratory regions. We postulate that changes in nNOS may play a role
in respiratory control plasticity.
biphasic response; respiration; roll-off; peripheral chemoreceptor; brain stem; neural plasticity
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