Maximal Oxygen Consumption Is Reduced in Aquaporin-1 Knockout Mice

We have measured maximal oxygen consumption ([Formula: see text] (O2,max)) of mice lacking one or two of the established mouse red-cell CO(2) channels AQP1, AQP9, and Rhag. We intended to study whether these proteins, by acting as channels for O(2), determine O(2) exchange in the lung and in the periphery. We found that [Formula: see text] (O2,max) as determined by the Helox technique is reduced by ~16%, when AQP1 is knocked out, but not when AQP9 or Rhag are lacking. This figure holds for animals respiring normoxic as well as hypoxic gas mixtures. To see whether the reduction of [Formula: see text] (O2,max) is due to impaired O(2) uptake in the lung, we measured carotid arterial O(2) saturation (S(O2)) by pulse oximetry. Neither under normoxic (inspiratory O(2) 21%) nor under hypoxic conditions (11% O(2)) is there a difference in S(O2) between AQP1(null) and WT mice, suggesting that AQP1 is not critical for O(2) uptake in the lung. The fact that the % reduction of [Formula: see text] (O2,max) is identical in normoxia and hypoxia indicates moreover that the limitation of [Formula: see text] (O2,max) is not due to an O(2) diffusion problem, neither in the lung nor in the periphery. Instead, it appears likely that AQP1(null) animals exhibit a reduced [Formula: see text] (O2,max) due to the reduced wall thickness and muscle mass of the left ventricles of their hearts, as reported previously. We conclude that very likely the properties of the hearts of AQP1 knockout mice cause a reduced maximal cardiac output and thus cause a reduced [Formula: see text] (O2,max), which constitutes a new phenotype of these mice.