Hypoxia alters the thermogenic response to cold in adult homeothermic and heterothermic rodents

Key points For small mammals living in a cold, hypoxic environment, supplying enough O-2 to sustain thermogenesis can be challenging. While heterothermic mammals are generally more tolerant of cold and hypoxia than homeothermic mammals, how they regulate O-2 supply and demand during progressive cooling in hypoxia is largely unknown. We show that as ambient temperature is reduced in hypoxia, body temperature falls in both homeotherms and heterotherms. In the homeothermic rat, a decrease in O-2 consumption rate and lung O-2 extraction accompany this fall in body temperature, despite a relative hyperventilation. Paradoxically, in heterothermic mice, hamsters and ground squirrels, body temperature decreases more than in the homeothermic rat, even though they maintain ventilation, increase lung O-2 extraction and maintain or elevate their O-2 consumption rates. Variation in cold and hypoxia tolerance among homeotherms and heterotherms reflects divergent strategies in how O-2 supply and demand are regulated under thermal and hypoxic challenges. Compared to homeothermic mammals, heterothermic mammals are reported to be exceptionally tolerant of cold and hypoxia. We hypothesised that this variation in tolerance stems from divergent strategies in how homeotherms and heterotherms regulate O-2 supply versus O-2 demand when exposed to hypoxia during progressive cooling. To test this hypothesis, we exposed adult rodents ranging in their degree of heterothermic expression (homeotherm: rats, facultative heterotherms: mice and hamsters, and obligate heterotherm: ground squirrels) to either normoxia (21% O-2) or environmental hypoxia (7% O-2), while reducing ambient temperature from 38 to 5 degrees C. We found that when ambient temperature was reduced in normoxia, all species increased their O-2 consumption rate and ventilation in parallel, maintaining a constant ventilatory equivalent and level of lung O-2 extraction. Surprisingly, body temperature fell in all species, significantly so in the heterotherms. When ambient temperature was reduced in hypoxia, however, the homeothermic rat decreased their O-2 consumption rate and lung O-2 extraction despite an increase in their ventilatory equivalent, indicative of a relative hyperventilation. Heterotherms (mice, hamsters and ground squirrels), on the other hand, decreased their ventilatory equivalent, but increased lung O-2 extraction and maintained or elevated their O-2 consumption rates, yet their body temperature fell even more than in the rat. These results are consistent with the idea that homeotherms and heterotherms diverge in the strategies they use to match O-2 supply and O-2 demand, and that enhanced cold and hypoxia tolerance in heterotherms may stem from an improved ability to extract O-2 from the inspired air.