PDGF-beta receptor expression and ventilatory acclimatization to hypoxia in the rat

Activation of platelet-derived growth factor-beta (PDGF-beta) receptors in the nucleus of the solitary tract (nTS) modulates the late phase of the acu te hypoxic ventilatory response (HVR) in the rat. We hypothesized that temp oral changes in PDGF-beta receptor expression could underlie the ventilator y acclimatization to hypoxia (VAH). Normoxic ventilation was examined in ad ult Sprague-Dawley rats chronically exposed to 10% O-2, and at 0, 1, 2, 7, and 14 days, Northern and Western blots of the dorsocaudal brain stem were performed for assessment of PDGF-beta receptor expression. Although no sign ificant changes in PDGF-beta receptor mRNA occurred over time, marked atten uation of PDGF-beta receptor protein became apparent after day 7 of hypoxic exposure. Such changes were significantly correlated with concomitant incr eases in normoxic ventilation, i.e., with VAH (r: -0.56, P < 0.005). In add ition, long-term administration of PDGF-BB in the nTS via osmotic pumps loa ded with either PDGF-BB (n = 8) or vehicle (Veh; n = 8) showed that althoug h 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. Furth ermore, 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-<beta> receptors in the dorsocaudal brain stem correlates with the magnitude of VAH. We speculate that the decreased expression of PDGF-beta receptors is mediated via internalization and degradation of the receptor r ather than by transcriptional regulation.