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 acute hypoxic ventilatory response (HVR) in the rat. We hypothesized that temporal changes in PDGF-beta receptor expression could underlie the ventilatory acclimatization to hypoxia (VAH). Normoxic ventilation was examined in adult 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 significant changes in PDGF-beta receptor mRNA occurred over time, marked attenuation of PDGF-beta 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-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 rather than by transcriptional regulation.
Alea
O A
OA
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Czapla
M A
MA
Lasky
J A
JA
Simakajornboon
N
N
Gozal
E
E
Gozal
D
D
D000222:Adaptation, Physiological; D000818:Animals; D000077214:Becaplermin; D015152:Blotting, Northern; D015153:Blotting, Western; D015870:Gene Expression; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008845:Microinjections; D010100:Oxygen / Q000008:administration & dosage; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D012123:Pulmonary Ventilation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta; D010100:Oxygen