Time-Dependence of Hyperoxia-Induced Impairment in Peripheral Chemoreceptor Activity and Glomus Cell Calcium Response

Abstract

In mammals, transient exposure to hyperoxia for a period of weeks during perinatal life leads to impairment of the ventilatory response to acute hypoxia, which may persist long beyond the duration of the hyperoxia exposure. The impairment of the ventilatory response to hypoxia is due to hyperoxia-induced reduction of carotid chemoreceptor sensitivity to hypoxia. We previously demonstrated that hyperoxia exposure in rats, from birth to two weeks of age, profoundly reduced carotid chemoreceptor single axonal responses to acute hypoxia challenge. However, the time course and mechanisms of this impairment are not known. Therefore, we investigated the effect of hyperoxia (FiO(2) = 0.6) on neonatal rats after 1, 3, 5, 8, and 14 days of exposure, starting at postnatal day 7. Carotid chemoreceptor single unit activities, nerve conduction time and glomus cell calcium responses to acute hypoxia were recorded in vitro. After 1 day in hyperoxia, single unit spiking rate in response to acute hypoxia was increased compared to controls. After 5 days in hyperoxia, the spiking response to acute hypoxia was significantly reduced compared to controls, nerve conduction time was lengthened and the glomus cell calcium response to acute hypoxia was reduced compared to controls. We conclude that perinatal exposure to hyperoxia, in rats, impairs the glomus cell calcium response (pre-synaptic) and the afferent nerve excitability (post-synaptic). The time course indicates that hyperoxia exerts these effects within days.