Long‐lasting increase in basal catecholamine secretion from neonatal adrenal medullary chromaffin cells by chronic intermittent hypoxia

Abstract

We previously reported that intermittent hypoxia (IH) facilitates hypoxia‐evoked catecholamine (CA) secretion from neonatal adrenal medullary chromaffin cells (AMC) in rat pups. Here, we examined the effects of repetitive hypoxia on CA secretion from AMC from IH exposed rat pups. Adrenal medullary slices were harvested from rat pups exposed to either IH or normoxia from ages P0‐P5, 8–9 hours/day. CA secretion was monitored by carbon fiber amperometry. In IH exposed pups, repetitive hypoxia (30s hypoxia followed by 90s normoxia × 5 episodes) facilitated CA secretion from AMC during each episode. Remarkably, basal CA secretion remained elevated for 30 min after terminating repetitive hypoxia. The long‐lasting increase in basal CA secretion was not seen in response to repetitive application of 40 mM K+. In striking contrast, in control pups, CA secretion during repetitive hypoxia was modest and after terminating the stimulus, promptly returned to basal levels. The long‐lasting increase in basal CA secretion in IH pups could be elicited in Ca2+ free medium and was prevented in presence of 10 μM ryanadine, which blocks ryanadine receptors (RyRs). These data suggest that neonatal IH results in long‐lasting activation of basal CA secretion by repetitive hypoxia, and this effect is mediated in part by RyRs and mobilization of intracellular Ca2+ (supported by HL‐90554, HL‐76537, HL‐86493 and HL‐089616).