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 4,000 m) while rats are absent at these altitudes, and there is 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 (3,600 m) and compared their hematocrit levels, right ventricular hypertrophy (index of pulmonary hypertension), and alveolar surface 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 (SpO₂) under ambient conditions, in response to exposure to sea level PO₂ (32% O₂ = 160 mmHg - 10 minutes), and hypoxia (18 and 15% O₂ = 90 and 75 mmHg - 10 minute 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 to rats, adult mice had similar levels of SpO₂, but lower hematocrit and hemoglobin levels, reduced right ventricular hypertrophy, and higher mass-corrected alveolar surface, 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 SpO₂ 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.