No abstract

Rats reared in hyperoxia hypoventilate in normoxia and exhibit progressive blunting of the hypoxic ventilatory response, changes which are at least partially attributed to abnormal carotid body development. Since the carotid body also responds to changes in arterial CO2/pH, we tested the hypothesis that developmental hyperoxia would attenuate the hypercapnic ventilatory response (HCVR) of neonatal rats by blunting peripheral and/or central chemoreceptor responses to hypercapnic challenges. Rats were reared in 21% O2 (Control) or 60% O2 (Hyperoxia) until studied at 4, 6–7, or 13–14 days of age. Hyperoxia rats had significantly reduced single-unit carotid chemoafferent responses to 15% CO2 at all ages; CO2 sensitivity recovered within 7 days after return to room air. Hypercapnic responses of CO2-sensitive neurons of the caudal nucleus tractus solitarius (cNTS) were unaffected by chronic hyperoxia, but there was evidence for a small decrease in neuronal excitability. There was also evidence for augmented excitatory synaptic input to cNTS neurons within brainstem slices. Steady-state ventilatory responses to 4% and 8% CO2 were unaffected by developmental hyperoxia in all three age groups, but ventilation increased more slowly during the normocapnia-to-hypercapnia transition in 4-day-old Hyperoxia rats. We conclude that developmental hyperoxia impairs carotid body chemosensitivity to hypercapnia, and this may compromise protective ventilatory reflexes during dynamic respiratory challenges in newborn rats. Impaired carotid body function has less of an impact on the HCVR in older rats, potentially reflecting compensatory plasticity within the CNS.

Rats reared in hyperoxia have smaller carotid bodies with reduced hypoxic responses. Since the carotid body (CB) also responds to changes in arterial CO2/pH, we hypothesized that developmental hyperoxia would alter CB and ventilatory responses to hypercapnia. Rats were reared in normoxia (21% O2) or hyperoxia (60% O2) until studied at 4, 6–7, or 13–14 days of age. Single‐unit chemoafferent activities were recorded in vitro from the soma of petrosal neurons with projections to the CB. Hyperoxia‐treated rats had significantly reduced carotid chemoafferent responses to hypercapnia (10% and 15% CO2) at all ages; CB CO2 sensitivity recovered within 7 days after return to room air. Ventilation was measured by plethysmography. Although steady‐state ventilatory responses to 4% and 8% CO2 were unaffected by developmental hyperoxia, ventilation increased more slowly during the normocapnia‐hypercapnia transition in hyperoxia‐treated rats. We conclude that developmental hyperoxia impairs CB chemosensitivity to both hypoxic and hypercapnic stimuli. Decreased CB CO2 sensitivity may compromise protective ventilatory reflexes during dynamic respiratory challenges. Supported by NIH grant P20 GM‐103423 (Maine INBRE).