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receptor expression and
ventilatory acclimatization to hypoxia in the rat
Constance S. Kaufman Pediatric Pulmonary Research Laboratory, Departments of 1 Pediatrics, 2 Physiology, and 3 Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112; and 4 Kosair Children's Hospital Research Institute, Departments of Pediatrics, Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky 40202
Activation of platelet-derived growth
factor-
(PDGF-) receptors in the nucleus of the solitary tract
(nTS) modulates the late phase of the acute hypoxic ventilatory
response (HVR) in the rat. We hypothesized that temporal changes in
PDGF- receptor expression could underlie the ventilatory
acclimatization to hypoxia (VAH). Normoxic ventilation was examined in
adult Sprague-Dawley rats chronically exposed to 10% O2,
and at 0, 1, 2, 7, and 14 days, Northern and Western blots of
the dorsocaudal brain stem were performed for assessment of
PDGF- receptor expression. Although no significant changes in
PDGF- receptor mRNA occurred over time, marked attenuation of
PDGF- receptor protein became apparent after day 7 of
hypoxic exposure. Such changes were significantly correlated with
concomitant increases in normoxic ventilation, i.e., with VAH
(r: 
0.56, P < 0.005). In addition,
long-term administration of PDGF-BB in the nTS via osmotic pumps
loaded with either PDGF-BB (n = 8) or vehicle (Veh;
n = 8) showed that although no significant changes in
the magnitude of acute HVR occurred in Veh over time, the typical
attenuation of HVR by PDGF-BB decreased over time. Furthermore, PDGF-BB
microinjections did not attenuate HVR in acclimatized rats at 7 and 14 days of hypoxia (n = 10). We conclude that decreased
expression of PDGF- receptors in the dorsocaudal brain stem
correlates with the magnitude of VAH. We speculate that the decreased
expression of PDGF- receptors is mediated via internalization and
degradation of the receptor rather than by transcriptional regulation.
growth factors; nucleus of solitary tract; brain stem; chronic
hypoxia; platelet-derived growth factor-
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