The influence of haemoglobin-O(2) affinity on aerobic capacity in hypoxia in high-altitude deer mice (Peromyscus maniculatus).

内容摘要

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 >4300 m elevation in the Rocky Mountains. Mice from populations native to high and low altitudes 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. Aerobic capacity for thermogenesis was measured in hypoxia after each of three pharmacological treatments: saline (control), efaproxiral (decreases Hb-O2 affinity) and cyanate (increases Hb-O2 affinity). High-altitude mice had greater aerobic capacity in hypoxia, in association with higher arterial O2 saturation ( S a O 2 ${{S}_{{\mathrm{a}}{{{\mathrm{O}}}_2}}}$ ) 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 and S a O 2 ${{S}_{{\mathrm{a}}{{{\mathrm{O}}}_2}}}$ are greater in high-altitude mice, in association with a greater capacity to extract and consume O2 in thermogenic tissues. KEY POINTS: Evolved increases in haemoglobin-O2 affinity are pervasive across high-altitude taxa, but the influence of such increases on aerobic capacity in hypoxia remains contentious. We examined whether the influence of haemoglobin-O2 affinity on aerobic capacity for thermogenesis is altered in high-altitude deer mice. Using pharmacological treatments to manipulate haemoglobin-O2 affinity, we found that aerobic capacity in hypoxia was greatest at higher affinities in high-altitude mice than in low-altitude mice. Skeletal muscle and brown adipose tissue had more oxidative and thermogenic phenotypes in high-altitude mice. These results suggest that the optimal haemoglobin-O2 affinity in hypoxia is greater in high-altitude deer mice, potentially resulting from a greater capacity to extract and consume O2 in active tissues.