Influence of hemoglobin-O₂ affnity on aerobic capacity in deer mice

High-altitude hypoxia can constrain tissue O 2 supply, and several high-altitude populations and species have evolved adaptations to overcome this challenge. Evolved increases in hemoglobin-O 2 (Hb-O 2 ) affnity are pervasive across high-altitude taxa, but the influence of such increases on aerobic capacity (maximal O 2 consumption) in hypoxia remains contentious. The influence of Hb-O 2 affnity on aerobic capacity in hypoxia could vary depending on other traits in the O 2 transport pathway, but this possibility is poorly understood. We examined this issue in deer mice ( Peromyscus maniculatus), which is found from sea level to >4300m altitude in the Rocky Mountains. Mice from populations native to high altitude and low altitude were born and raised to adulthood in captivity. Low-altitude mice (n=14) were acclimated to warm (25°C) normoxia, and high-altitude mice (n=14) were acclimated to cold (5°C) hypoxia (~12 kPa O 2 ) for 6 weeks, creating two groups with very different capacities for O 2 transport in hypoxia. Aerobic capacity for thermogenesis (VO 2 max) was then measured in hypoxia after each of three pharmacological treatments to manipulate Hb-O 2 affnity: saline (control); efaproxiral, a negative allosteric regulator that decreases Hb-O 2 affnity; and sodium cyanate, which covalently modifies Hb and increases Hb-O 2 affnity. In control conditions, high-altitude mice had higher VO 2 max and arterial O 2 saturation (SaO 2 ) in hypoxia and higher Hb-O 2 affnity (lower P 50 ) than low-altitude mice. Efaproxiral reduced SaO 2 and led to similar decreases in VO 2 max in both populations. Sodium cyanate increased SaO 2 in hypoxia in both populations. However, this was only associated with an increase in VO 2 max in 7 of 14 high-altitude mice and 4 of 14 low-altitude mice. Our results suggest that Hb-O 2 affnity may be optimal for aerobic capacity in hypoxia in high-altitude mice, and that reductions in Hb-O 2 affnity reduce performance. Supported by NSERC of Canada. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.