Effects of Hemoglobin-O₂ Affinity on Breathing and Gas Exchange in Deer Mice

AbstractEvolved increases in hemoglobin (Hb)-O₂ affinity are common across high-altitude mammals and birds, but the downstream physiological effects of such increases remain poorly understood. In deer mice (Peromyscus maniculatus), the genetic variants of α- and β-globin in high-altitude populations are also associated with evolved changes in breathing pattern and the hypoxic ventilatory response, raising the question of whether chronic increases in Hb-O₂ affinity affect breathing and gas exchange in this species. We tested this possibility in lab-raised deer mice from low-altitude populations by pharmacologically increasing Hb-O₂ affinity over 4 wk using cyanate. Treatments were conducted during adulthood and early postnatal development in normoxia to examine whether the influence of Hb-O₂ affinity is life stage specific. Breathing, arterial O₂ saturation, and aerobic metabolism (O₂ consumption rate) were then measured in normoxia, hypoxia (10% O₂), and hypoxic hypercarbia (10% O₂, 3% CO₂). Cyanate-treated mice experienced pronounced decreases in O₂ pressure at 50% Hb saturation compared to saline-treated controls and exhibited corresponding increases in arterial O₂ saturation in hypoxic conditions in both adults and juveniles. Total ventilation increased and metabolism decreased in hypoxia and hypoxic hypercarbia, but cyanate had little to modest effects on these responses. Effects of cyanate on breathing frequency, tidal volume, and the relationship between total ventilation and tidal volume (an indicator of breathing pattern) were also modest and inconsistent between adults and juveniles. The results suggest that chronic increases in Hb-O₂ affinity have no clear and consistent effects on breathing pattern or the hypoxic ventilatory response.