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J Appl Physiol (August 18, 2005). doi:10.1152/japplphysiol.01205.2004
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Submitted on October 25, 2004
Accepted on August 17, 2005

The Effects of Chronic Hypoxia on MK801-Induced Changes in the Acute Hypoxic Ventilatory Response

Stephen G. Reid1* and Frank L. Powell2

1 Division of Physiology, Department of Medicine, University of California, San Diego, San Diego, CA, USA; Department of Life Sciences, University of Toronto at Scarborough, Toronto, ONTARIO, Canada
2 Division of Physiology, Department of Medicine, University of California, San Diego, San Diego, CA, USA

* To whom correspondence should be addressed. E-mail: sgreid{at}utsc.utoronto.ca.

Chronic hypoxia increases the sensitivity of the central nervous system to afferent input from carotid body chemoreceptors. We hypothesized that this involves NMDA receptor-mediated mechanisms and predicted that chronic hypoxia would change the effect of the NMDA receptor blocker dizocilpine (MK801) on the poikilocapnic hypoxic ventilatory response (HVR). Male Sprague-Dawley rats were studied before and after acclimatization to hypoxia (PIO2 = 70 Torr for 9 days). We measured ventilation (VI) and the HVR before and after systemic MK801 treatment(3mg/kg i.p.). MK801 resulted in a constant respiratory frequency (fR ~ 175 min-1) during acute exposure to both 10% O2 and 30% O2, both before and after acclimatization. MK801 had no effect on tidal volume (VT) before acclimatization but it significantly decreased VT when the animals were breathing 10% O2 after acclimatization. The net effect of MK801 was to eliminate the O2-sensitivity of VI both before (via changes in fR) and after (via changes in VT) acclimatization. Hence, chronic hypoxia altered the effect of MK801 on the acute HVR, primarily because of increased effects on tidal volume. This indicates changes in NMDA receptor-mediated neurotransmission may be involved in ventilatory acclimatization to hypoxia. However, further experiments are necessary to determine the precise location of such plasticity in the central nervous system.




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