title: Developmental hyperoxia alters CNS mechanisms underlying hypoxic ventilatory depression in neonatal rats.
abstract: Newborn mammals exhibit a biphasic hypoxic ventilatory response (HVR), but the relative contributions of carotid body-initiated CNS mechanisms versus central hypoxia on ventilatory depression during the late phase of the HVR are not well understood. Neonatal rats (P4-5 or P13-15) were treated with a nonselective P2 purinergic receptor antagonist (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, or PPADS; 125mgkg(-1), i.p.) to pharmacologically denervate the peripheral chemoreceptors. At P4-5, rats reared in normoxia showed a progressive decline in ventilation during a 10-min exposure to 12% O2 (21-28% decrease from baseline). No hypoxic ventilatory depression was observed in the older group of neonatal rats (i.e., P13-15), suggesting that the contribution of central hypoxia to hypoxic ventilatory depression diminishes with age. In contrast, rats reared in moderate hyperoxia (60% O2) from birth exhibited no hypoxic ventilatory depression at either age studied. Systemic PPADS had no effect on the ventilatory response to 7% CO2, suggesting that the drug did not cross the blood-brain barrier. These findings indicate that (1) CNS hypoxia depresses ventilation in young, neonatal rats independent of carotid body activation and (2) hyperoxia alters the development of CNS pathways that modulate the late phase of the hypoxic ventilatory response.
authors.affiliation: Department of Biology, Bates College, Lewiston, ME 04240, USA.
authors.forename: Corey B
authors.initials: CB
authors.lastname: Hill
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Grandgeorge
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Bavis
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017763:Autonomic Denervation / Q000379:methods; D002490:Central Nervous System / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D018496:Hyperoxia / Q000503:physiopathology*; D008297:Male; D010975:Platelet Aggregation Inhibitors; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology; D058921:Purinergic P2Y Receptor Antagonists / Q000633:toxicity; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D015656:Respiratory Mechanics / Q000502:physiology*; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate
keywords: Biphasic hypoxic ventilatory response; Carotid body denervation; Control of breathing; Development; Hypoxic ventilatory depression; Phenotypic plasticity