Developmental hyperoxia alters CNS mechanisms underlying hypoxic ventilatory depression in neonatal rats

•Neonatal rats reared in hyperoxia have a sustained HVR younger than expected.•We used systemic PPADS to isolate contributions of CNS hypoxia.•Control rats exhibit hypoxic ventilatory depression at P4-5 but not at P13-15.•Hyperoxia-reared rats exhibited no hypoxic ventilatory depression at either age.•Developmental hyperoxia elicits plasticity in the CNS response to hypoxia.

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; 125 mg kg−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.