Ventilatory acclimatization to hypoxia in deer mice native to high altitudes

Abstract

Hypoxia at high altitudes constrains O2 supply to support metabolism, thermoregulation in the cold, and the aerobic scope needed for exercise. Many highland taxa appear to have physiological specializations for overcoming these challenges, but relatively little is known about the importance of hypoxia acclimation responses in high‐altitude natives, such as ventilatory acclimatization to hypoxia (VAH) and erythropoiesis. Highland taxa often possess a high haemoglobin‐O2 binding affinity, which safeguards arterial O2 saturation (SaO2) and tissue O2 delivery in hypoxia, but could foreseeably affect hypoxia acclimation responses. We examined this issue by comparing captive populations of deer mice (Peromyscus maniculatus) from high and low altitudes. Mice from each population were acclimated to normoxia and moderate hypoxia (12 kPa O2, simulating the PO2 at the native altitude of highlanders at 4300m) for 6–8 weeks. Highland mice were also acclimated to more severe hypoxia (9 kPa, the PO2 at ~7000m), which induces the same SaO2 in highlanders that lowlanders experience at 12 kPa. In lowlanders, hypoxia acclimation augmented the hypoxic ventilatory response (HVR), increased SaO2 in hypoxia, blunted the hypoxic depression of body temperature, increased blood [haemoglobin], and induced right ventricle hypertrophy (a sign of maladaptive pulmonary hypertension). Hypoxia acclimation had little effect on the HVR in highlanders, such that the hypoxic control of breathing appeared to be fixed like that in hypoxia‐acclimated lowlanders. Right ventricle hypertrophy did not occur in either moderate or severe hypoxia in highlanders, suggesting that they have blunted hypoxic pulmonary vasoconstriction and hypertension. The increase in blood [haemoglobin] was lower in highlanders than in lowlanders at 12 kPa, but highlanders mounted a robust increase in severe hypoxia (9 kPa), suggesting that differences in SaO2 and not the erythropoietic process contribute to differences in blood [haemoglobin] between populations. Therefore, high‐altitude adaptation appears to have blunted several hypoxia acclimation responses in deer mice.Support or Funding InformationSupported by NSERC of Canada.