Divergent physiological responses in laboratory rats and mice raised at high altitude

Ecological studies show that mice can be found at high altitude (HA - up to 4000 m) while rats are absent at these altitudes, and there are no data to explain this discrepancy. We used adult laboratory rats and mice that have been raised for more than 30 generations in La Paz, Bolivia (3600 m), and compared their hematocrit levels, right ventricular hypertrophy (index of pulmonary hypertension) and alveolar surface area in the lungs. We also used whole-body plethysmography, indirect calorimetry and pulse oxymetry to measure ventilation, metabolic rate (O2 consumption and CO2 production), heart rate and pulse oxymetry oxygen saturation (pO2 ,sat) under ambient conditions, and in response to exposure to sea level PO2 (32% O2=160 mmHg for 10 min) and hypoxia (18% and 15% O2=90 and 75 mmHg for 10 min each). The variables used for comparisons between species were corrected for body mass using standard allometric equations, and are termed mass-corrected variables. Under baseline, compared with rats, adult mice had similar levels of pO2 ,sat, but lower hematocrit and hemoglobin levels, reduced right ventricular hypertrophy and higher mass-corrected alveolar surface area, tidal volume and metabolic rate. In response to sea level PO2 and hypoxia, mice and rats had similar changes of ventilation, but metabolic rate decreased much more in hypoxia in mice, while pO2 ,sat remained higher in mice. We conclude that laboratory mice and rats that have been raised at HA for >30 generations have different physiological responses to altitude. These differences might explain the different altitude distribution observed in wild rats and mice.