Evolved changes in breathing and CO2 sensitivity in deer mice native to high altitudes

We examined the control of breathing by O₂ and CO₂ in deer mice native to high altitude to help uncover the physiological specializations used to cope with hypoxia in high-altitude environments. Highland deer mice ( Peromyscus maniculatus) and lowland white-footed mice ( P. leucopus) were bred in captivity at sea level. The first and second generation progeny of each population was raised to adulthood and then acclimated to normoxia or hypobaric hypoxia (12 kPa O₂, simulating hypoxia at ~4,300 m) for 6-8 wk. Ventilatory responses to poikilocapnic hypoxia (stepwise reductions in inspired O₂) and hypercapnia (stepwise increases in inspired CO₂) were then compared between groups. Both generations of lowlanders appeared to exhibit ventilatory acclimatization to hypoxia (VAH), in which hypoxia acclimation enhanced the hypoxic ventilatory response and/or made the breathing pattern more effective (higher tidal volumes and lower breathing frequencies at a given total ventilation). In contrast, hypoxia acclimation had no effect on breathing in either generation of highlanders, and breathing was generally similar to hypoxia-acclimated lowlanders. Therefore, attenuation of VAH may be an evolved feature of highlanders that persists for multiple generations in captivity. Hypoxia acclimation increased CO₂ sensitivity of breathing, but in this case, the effect of hypoxia acclimation was similar in highlanders and lowlanders. Our results suggest that highland deer mice have evolved high rates of alveolar ventilation that are unaltered by exposure to chronic hypoxia, but they have preserved ventilatory sensitivity to CO₂.