Renal carbonic anhydrase inhibition reduces high altitude sleep periodic breathing

The efficacy of carbonic anhydrase (CA) inhibitors in amelioration of periodic breathing during sleep at high altitude is not fully understood. Although CA is present in a number of tissues, we hypothesized that selective renal CA inhibition without physiologically important inhibition of other tissue CA, may be sufficient alone by its generation of a mild metabolic acidosis to stimulate ventilation and prevent periodic breathing. We studied benzolamide (3 mg/kg), a selective inhibitor of renal CA, in 4 climbers on ventilation and ventilatory responses at sea level and on arterial O2 saturation (SaO2%) and periodic breathing during sleep at altitude. At sea level, ventilation increased and PaO2 rose accompanied by a mild metabolic acidosis. The isocapnic hypoxic ventilatory response was unchanged but the hyperoxic hypercapnic ventilatory response rose 40%. At high altitude (4400 m), daytime SaO2% improved from 81 to 85 and venous plasma HCO3- fell from 18.9 to 14.8 mM. During sleep, mean SaO2% rose from 76 to 80 and periodic breathing decreased 75%. We conclude that metabolic acidosis occurring with all CA inhibitors is one of the major stimulant actions of these drugs on ventilation while awake and during sleep at high altitude.