FigShare_Data HbO2 JoP 50 (KMG).xlsx

High-altitude hypoxia constrains tissue O2 supply, but several high-altitude populations have evolved adaptations to overcome this challenge. Evolved increases in haemoglobin-O2 (Hb-O2) affinity are pervasive across high-altitude taxa, but the influence of such increases on aerobic capacity in hypoxia remains contentious. The influence of Hb-O2 affinity could depend on the capacity to extract O2 from the blood, but this possibility is poorly understood. We examined this issue in deer mice (Peromyscus maniculatus), which are found from sea level to >4300m elevation in the Rocky Mountains. Mice from populations native to high- and low-altitude were born and raised in captivity. Low-altitude mice were acclimated to warm (25°C) normoxia and high-altitude mice were acclimated to cold (5°C) hypoxia (~12 kPa O2), creating two groups with distinct capacities for O2 transport in hypoxia. Aerobic capacity for thermogenesis was measured in hypoxia after each of three pharmacological treatments: saline (control), efaproxiral (decreases Hb-O2 affinity), and sodium cyanate (increases Hb-O2 affinity). High-altitude mice generally had greater aerobic capacity in hypoxia, in association with higher arterial O2 saturation and lower P50 (O2 pressure at 50% Hb saturation) in most conditions. The P50 at which aerobic capacity was greatest was lower in high-altitude mice than in low-altitude mice. High-altitude mice also had greater uncoupling protein 1 (UCP-1) content in brown adipose tissue and greater cytochrome oxidase activity in gastrocnemius muscle. These results suggest that optimal Hb-O2 affinity is greater in high-altitude deer mice, in association with a greater capacity to extract and consume O2 in thermogenic tissues.