Comparative analysis of neonatal and adult rat carotid body responses to chronic intermittent hypoxia

Abstract

Previous studies suggest that carotid body responses to long-term changes in environmental oxygen differ between neonates and adults. In the present study we tested the hypothesis that the effects of chronic intermittent hypoxia (CIH) on the carotid body differ between neonates and adult rats. Experiments were performed on neonatal (1-10 days) and adult (6-8 wk) males exposed either to CIH (9 episodes/h; 8 h/day) or to normoxia. Sensory activity was recorded from ex vivo carotid bodies. CIH augmented the hypoxic sensory response (HSR) in both groups. The magnitude of CIH-evoked hypoxic sensitization was significantly greater in neonates than in adults. Seventy-two episodes of CIH were sufficient to evoke hypoxic sensitization in neonates, whereas as many as 720 CIH episodes were required in adults, suggesting that neonatal carotid bodies are more sensitive to CIH than adult carotid bodies. CIH-induced hypoxic sensitization was reversed in adult rats after reexposure to 10 days of normoxia, whereas the effects of neonatal CIH persisted into adult life (2 mo). Acute intermittent hypoxia (IH) evoked sensory long-term facilitation of the carotid body activity (sensory LTF, i.e., increased baseline neural activity following acute IH) in CIH-exposed adults but not in neonates. The effects of CIH were associated with hyperplasia of glomus cells in neonatal but not in adult carotid bodies. These observations demonstrate that responses to CIH differ between neonates and adults with regard to the magnitude of sensitization of HSR, susceptibility to CIH, induction of sensory LTF, reversibility of the responses, and morphological remodeling of the chemoreceptor tissue.

Carotid sinus nerve stimulation, but not intermittent hypoxia, induces respiratory LTF in adult rats exposed to neonatal intermittent hypoxia

“…We have recently reported in rat pups that n-IH during 10 days from birth increases ventilatory response to brief (50 s) hypoxic exposure (25), strongly suggesting higher sensitivity of peripheral chemoreceptors as reported by in vitro recordings (47), while the ventilatory LTF was suppressed (25), as reported by Reeves et al (50) in 2-mo-old rats raised under n-IH for 30 days from birth. Accordingly, this model might be useful to determine whether n-IH-related alterations in respiratory regulation persist into adulthood and alter the central integration of peripheral chemoreceptor inputs.…”

“…Accordingly, our results strongly suggest that hypoxic sensitivity in peripheral chemoreceptors was not altered in n-IH rats. Contrastingly, in rat pups, hypoxic ventilatory response (25) and carotid body response to hypoxia (47) were increased following chronic intermittent hypoxic exposure. On the other hand, a similar model of n-IH induced a persistent enhancement in the hypoxic response of the superfused in vitro carotid body/CSN preparation from 60-day-old rats (47) while we studied in vivo rats at 90 days of age.…”

“…Over the past years, several studies have documented that alterations in environmental oxygen levels during development lead to important changes of the respiratory control system (4). A particular importance has been given to intermittent hypoxic exposure (38,47,50) because it may be used in laboratory animals to reproduce some of the effects encountered in human newborn suffering from apneas, which remains one of the major causes of morbidity in preterm neonates (10). Recent studies have shown that neonatal intermittent hypoxia (n-IH) exposure for 10 days after birth enhances the carotid body response to hypoxia as recorded using the in vitro carotid body/carotid sinus nerve (CSN) preparation in 2 mo-old rats (47).…”

“…A particular importance has been given to intermittent hypoxic exposure (38,47,50) because it may be used in laboratory animals to reproduce some of the effects encountered in human newborn suffering from apneas, which remains one of the major causes of morbidity in preterm neonates (10). Recent studies have shown that neonatal intermittent hypoxia (n-IH) exposure for 10 days after birth enhances the carotid body response to hypoxia as recorded using the in vitro carotid body/carotid sinus nerve (CSN) preparation in 2 mo-old rats (47). It has also been reported that rats raised during 30 days from birth under IH have elevated minute ventilation, but showed a blunted respiratory response to hypoxia and reduced expression of respiratory plasticity such as the one evoked by successions of hypoxic episodes (50) [long-term facilitation (LTF); see Refs.…”

Epigenetic regulation of hypoxic sensing disrupts cardiorespiratory homeostasis

“…Carotid body sensitivity to hypoxia is reset after birth and this effect is modulated by chronic hypoxia (4)(5)(6). Neonatal rats exposed to IH showed exaggerated carotid body and ventilatory responses to hypoxia (7,8). Catecholamine secretion from the adrenal medulla is another important homeostatic mechanism that preserves cardiovascular function under hypoxia (9,10).…”