Effects of oxygen availability on maximum aerobic performance inMus musculusselected for basal metabolic rate or aerobic capacity

Maximum aerobic metabolism cannot increase indefinitely in response to demands for ATP production and, therefore, must be constrained by one (or many) of the steps of the oxygen transport and utilization pathways. To elucidate those constraints we compared peak metabolic rate elicited by running (V(.)(O₂,run)) in hypoxia (14% O₂), normoxia (21% O₂) and hyperoxia (30% O₂) of laboratory mice divergently selected for low and high basal metabolic rate (L-BMR and H-BMR, respectively), mice selected for maximum metabolic rate elicited by swimming (V(.)(O₂,swim)) and mice from unselected lines. In all line types (V(.)(O₂,run)) was lowest in hypoxia, intermediate in normoxia and highest in hyperoxia, which suggests a 'central' limitation of oxygen uptake or delivery instead of a limit set by cellular oxidative capacity. However, the existence of a common central limitation is not in agreement with our earlier studies showing that selection on high V(.)(O₂,swim) (in contrast to selection on high BMR) resulted in considerably higher oxygen consumption during cold exposure in a He-O₂ atmosphere than V(.)(O₂,run). Likewise, between-line-type differences in heart mass and blood parameters are inconsistent with the notion of central limitation. Although responses of V(.)(O₂,run) to hypoxia were similar across different selection regimens, the selection lines showed contrasting responses under hyperoxic conditions. V(.)(O₂,run) in the H-BMR line type was highest, suggesting that selection on high BMR led to increased cellular oxidative capacity. Overall, between-line-type differences in the effect of the oxygen partial pressure on V(.)(O₂,run) and in the components of O₂ flux pathways are incompatible with the notion of symmorphosis. Our results suggest that constraints on V(.)(O₂,max) are context dependent and determined by interactions between the central and peripheral organs and tissues involved in O₂ delivery.