Evolved changes in reflex control of the cardiovascular system in deer mice native to high altitude

The cold and hypoxic conditions at high altitude place high demands on the cardiovascular system to sustain circulatory O2 transport. High-altitude natives have evolved to overcome cold hypoxia, but the cardiovascular mechanisms involved remain poorly understood in most taxa. Here, we investigated the evolved changes in reflex control of cardiovascular function in deer mice (Peromyscus maniculatus) native to high altitude. High- and low-altitude populations of deer mice were each bred in captivity and then chronically acclimated to warm normoxia (25°C, ∼20 kPa O2) or cold hypoxia (5°C, 12 kPa O2) for 6-8 weeks. Cardiovascular function was measured in vivo using physiological telemeters, complemented by wire myography to examine vascular function ex vivo. High-altitude mice acclimated to cold hypoxia exhibited greater heart rates and were better able to maintain blood pressure in moderate and severe hypoxia, in association with less pronounced depression of metabolism and body temperature. High-altitude mice also exhibited greater baroreflex sensitivity than low-altitude mice across acclimation environments, as reflected by greater changes in heart rate and smaller changes in arterial blood pressure during pharmacological manipulations. Mesenteric arteries from each population exhibited similar ex vivo smooth muscle contractions in response to phenylephrine (α1-adrenoceptor agonist), and similar endothelium-dependent relaxation in response to acetylcholine, suggesting that evolved changes in the baroreflex arise from adjustments in autonomic control of the heart and/or other resistance vessels. These evolved changes in cardiovascular function and reflex control may be valuable for supporting high metabolic rates in the cold and hypoxic environment at high altitude.