PDGF-beta receptor expression in the dorsocaudal brainstem parallels hypoxic ventilatory depression in the developing rat

The temporal trajectory of platelet-derived growth factor (PDGF)-beta recep tor activation within the dorsocaudal brainstem parallels that of the mild hypoxic ventilatory depression (HVD) seen in adult rats. We hypothesized th at enhanced PDGF-beta receptor activity may account for the particularly pr ominent HVD of developing mammals. To study this issue, 2-, 5-, 10-, and 20 -d-old rats underwent hypoxic challenges (10% O-2 for 30 min) after pretrea tment with either vehicle (Veh) or the selective PDGF-beta receptor antagon ist CGP57148B (intraperitoneal 100 mg/kg). The developmental characteristic s and magnitude of the peak hypoxic ventilatory response (HVR) were not mod ified by the PDGF-beta receptor blocker. However, HVD was markedly I attenu ated by CGP57148B, and such effect, although still present, gradually abate d with increasing postnatal age [p < 0.001, analysis of variance (ANOVA)]. Hypercapnic ventilatory responses were not affected by CGP57148B. The expre ssion of PDGF-beta receptor in the dorsocaudal brainstem was assessed by im munoblotting and confirmed progressively decreasing expression with maturat ion. We conclude that PDGF-beta receptor activation during hypoxia is an im portant contributor to HVD at all postnatal ages but more particularly in t he immature rat.