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 receptor activation within the dorsocaudal brainstem parallels that of the mild hypoxic ventilatory depression (HVD) seen in adult rats. We hypothesized that enhanced PDGF-beta 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% O(2) for 30 min) after pretreatment with either vehicle (Veh) or the selective PDGF-beta 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-beta 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-beta receptor in the dorsocaudal brainstem was assessed by immunoblotting and confirmed progressively decreasing expression with maturation. We conclude that PDGF-beta receptor activation during hypoxia is an important contributor to HVD at all postnatal ages but more particularly in the immature rat.
Vlasic
V
V
Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville School of Medicine, 570 S. Preston Street, Louisville, KY 40202, U.S.A.
Simakajornboon
N
N
Gozal
E
E
Gozal
D
D
D000818:Animals; D001549:Benzamides; D001933:Brain Stem / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D006935:Hypercapnia / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D000068877:Imatinib Mesylate; D015151:Immunoblotting; D010879:Piperazines / Q000494:pharmacology; D012123:Pulmonary Ventilation / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta