Acetazolamide affects breathing differently in ICR and C57 mice

Acetazolamide (ACZ) administration was compared on ventilation in outbred male ICR Swiss Webster (ICR) and inbred C57BL/6J (C57) mice, used in development of transgenic strains. We hypothesized that in both strains ACZ would affect breathing similarly. Mice received intraperitoneally vehicle and the next week ACZ (40 mg/kg), and were exposed to air for 90 min, followed by 5-min exposure to10% O2, air for 15 min, and to 5 min of 5% CO2 in O2. Ventilation was evaluated using plethysmography. ACZ stimulated ventilation in both stains exposed to air. C57 mice minimally increased frequency and tidal volume, whereas ICR mice markedly increased frequency. Strain differences in the ventilatory pattern in response to hypoxia and hypercapnia occurred. ACZ-treated ICR mice decreased hypoxic responsiveness to 50% of vehicle values, whereas ACZ had no effect in C57 mice. ACZ decreased hypercapnic ventilatory responsiveness in both strains. Differential effects of ACZ breathing in these two strains suggest that genetic factors modulate its effect on breathing.