Catecholamine secretion from the adrenal medulla is blunted in high‐altitude deer mice ( Peromyscus maniculatus )

Chronic hypoxia stimulates the sympathetic nervous system and adrenal catecholamine (CAT) secretion, which helps to protect vital organs during low oxygen conditions. However, chronic sympathetic activation has also been associated with systemic and pulmonary dysfunction related to the extended elevation of circulating CATs. In this study, we compared the effects of chronic hypoxia exposure (6–8 weeks, 12 kPa O 2 ) on CAT secretion from adrenomedullary chromaffin cells (AMCs) obtained from low‐versus high‐altitude populations of deer mice. Under normoxic conditions, acetylcholine released from the splanchnic nerve acts on nicotinic acetylcholine receptors (AChR) in the adrenal medulla, and results in CAT secretion into the circulation. Using carbon fiber amperometry, CAT secretion was measured in thin adrenal slices exposed to the AChR agonist, nicotine (10 or 50 uM). CAT secretion in response to low doses of nicotine (10 uM) was blunted in AMCs of lowland mice after chronic hypoxia exposure, but restored in hypoxic lowlanders when higher concentrations of nicotine (50 uM) were applied. In comparison to lowlanders CAT secretion from AMCs of the highland population, acclimated to either normoxic or hypoxic conditions, was significantly lower in response to both high and low doses of nicotine. The prominent reduction of CAT secretion in the adrenal medulla of the highland population across both environmental conditions suggests an alteration in nicotinic AChR function and/or a reduction in CAT secretory function in these mice. Further examination of AMCs in low‐versus high‐altitude deer mice revealed lower expression of key enzymes in catecholamine synthesis (particularly DOPA decarboxylase), as well as lower plasma levels of adrenaline, in the highland population. Our findings suggest that high‐altitude adaption in deer mice suppresses catecholamine secretion from the adrenal gland in hypoxia, which appears to involve a reduction in catecholamine synthesis and storage. Support or Funding Information Funded by the Natural Sciences and Engineering Research Council (NSERC) of Canada. Angela L Scott is a NSERC Postdoctoral Fellow.