Chronic intermittent hypoxia induces hypoxia‐evoked catecholamine efflux in adult rat adrenal medulla via oxidative stress

Abstract

Chronic intermittent hypoxia (CIH) augments physiological responses to low partial pressures of O 2 in the arterial blood. Adrenal medullae from adult rats, however, are insensitive to direct effects of acute hypoxia. In the present study, we examined whether CIH induces hypoxic sensitivity in the adult rat adrenal medulla and, if so, by what mechanism(s). Experiments were performed on adult male rats exposed to CIH (15 s of 5% O 2 followed by 5 min of 21% O 2 ; 9 episodes h −1 ; 8 h d −1 ; for 3 or 10 days) or to comparable, cumulative durations of continuous hypoxia (CH; 4 h of 7% O 2 followed by 20 h of 21% O 2 for 1 or 10 days). Noradrenaline (NA) and adrenaline (ADR) effluxes were monitored from ex vivo adrenal medullae. In adrenal medullae of rats exposed to CIH, acute hypoxia evoked robust NA and ADR effluxes, whereas these responses were absent in control rats or in those exposed to CH for 1 or 10 days. Hypercapnia (10% CO 2 ; either acidic, pH 6.8, or isohydric, pH 7.4) was ineffective in eliciting catecholamine (CA) efflux from control, CIH or CH rats. Nicotine (100 μM) evoked NA and ADR effluxes in control rats, and this response was abolished in CIH but not in CH rats. Systemic administration of 2-deoxyglucose depleted ADR content in control rats, and CIH attenuated this response, indicating downregulation of neurally regulated CA secretion. Cytosolic and mitochondrial aconitase enzyme activities decreased in CIH adrenal medullae, suggesting increased generation of superoxide anions. Systemic administration of antioxidants reversed the effect of CIH on the adrenal medulla. Rats exposed to CIH exhibited increased blood pressures and elevated plasma CA, and antioxidants abolished these responses. These observations demonstrate that CIH induces hypoxic sensing in the adult rat adrenal medulla via mechanisms involving increased generation of superoxide anions and suggest that hypoxia-evoked CA efflux from the adrenal medulla contributes, in part, to elevated blood pressure and plasma CA.

Epigenetic regulation of hypoxic sensing disrupts cardiorespiratory homeostasis

“…Exaggerated hypoxic sensing of carotid body and adrenal chromaffin cells in neonates by IH is attributed to increased oxidative stress (12,14). IH also augments hypoxic responses of the carotid body and adrenal medulla in adult rats (15,16), which is completely reversed following reoxygenation (15). In striking contrast, in neonates the augmented hypoxic sensitivity that is induced by IH persists into adulthood (8,12,14).…”

Effects of obstructive sleep apnoea on heart rhythm

“…In addition, ROS may not only have a direct effect on intracellular structures, but also promote the sympathetic response in carotid bodies and the adrenal medulla's production of catecholamines in response to hypoxia [19,38].…”

Effects of age on ACTH, corticosterone, glucose, insulin, and mRNA levels during intermittent hypoxia in the neonatal rat

“…Pups instrumented with an Oximeter collar were used for plasma measurements. Pups instrumented for body temperature measurements were not used for plasma or tissue analyses.The IH protocol was based on previously described models (15,29). IH was composed of six cycles consisting of the following: 1) a decrease in chamber %O 2 (FIO 2 ) using high-flow (Ͼ20 l/min) nitrogen until 3% was reached (ϳ90 s), 2) a hold at 3% for 30 s (trough), 3) an increase in FI O 2 using high-flow room air (Ͼ20 l/min) until 20% was reached (ϳ90 s), and 4) a hold at 21% O 2 for 5 min (peak).…”