Circulatory mechanisms underlying adaptive increases in thermogenic capacity in high-altitude deer mice

We examined the circulatory mechanisms underlying adaptive increases in thermogenic capacity in deer mice ( Peromyscus maniculatus ) native to the cold hypoxic environment at high altitudes. Deer mice from high- and low-altitude populations were born and raised in captivity to adulthood, and then acclimated to normoxia or hypobaric hypoxia (simulating hypoxia at ∼4300 m). Thermogenic capacity [maximal O 2 consumption ( V̇ O 2 ,max ), during cold exposure] was measured in hypoxia, along with arterial O 2 saturation ( S a O 2 ) and heart rate ( f H ). Hypoxia acclimation increased V̇ O 2 ,max by a greater magnitude in highlanders than in lowlanders. Highlanders also had higher S a O 2  and extracted more O 2 from the blood per heartbeat (O 2 pulse= V̇ O 2 ,max / f H ). Hypoxia acclimation increased f H , O 2 pulse and capillary density in the left ventricle of the heart. Our results suggest that adaptive increases in thermogenic capacity involve integrated functional changes across the O 2 cascade that augment O 2 circulation and extraction from the blood.