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

Abstract

The temporal trajectory of platelet-derived growth factor (PDGF)-β receptor activation within the dorsocaudal brainstem parallels that of the mild hypoxic ventilatory depression (HVD) seen in adult rats. We hypothesized that enhanced PDGF-β receptor activity may account for the particularly prominent HVD of developing mammals. To study this issue, 2-, 5-, 10-, and 20-d-old rats underwent hypoxic challenges (10% O2 for 30 min) after pretreatment with either vehicle (Veh) or the selective PDGF-β receptor antagonist CGP57148B (intraperitoneal 100 mg/kg). The developmental characteristics and magnitude of the peak hypoxic ventilatory response (HVR) were not modified by the PDGF-β receptor blocker. However, HVD was markedly attenuated by CGP57148B, and such effect, although still present, gradually abated with increasing postnatal age [p < 0.001, analysis of variance (ANOVA)]. Hypercapnic ventilatory responses were not affected by CGP57148B. The expression of PDGF-β receptor in the dorsocaudal brainstem was assessed by immunoblotting and confirmed progressively decreasing expression with maturation. We conclude that PDGF-β receptor activation during hypoxia is an important contributor to HVD at all postnatal ages but more particularly in the immature rat.