CARBONIC-ANHYDRASE AND CONTROL OF BREATHING - DIFFERENT EFFECTS OF BENZOLAMIDE AND METHAZOLAMIDE IN THE ANESTHETIZED CAT

1. The effect of inhibition of erythrocyte carbonic anhydrase on the v entilatory response to CO2 was studied by administering benzolamide (7 0 mg kg(-1), I.V.), an inhibitor which does not cross the blood-brain barrier, to carotid body denervated cats which were anaesthetized with chloralose-urethane. 2. In the same animals the effect on the ventila tory response to CO2 of subsequent inhibition of central nervous syste m (CNS) carbonic anhydrase was studied by infusing methazolamide (20 m g kg(-1)), an inhibitor which rapidly penetrates into brain tissue. 3. The results show that inhibition of erythrocyte carbonic anhydrase by benzolamide leads to a decrease in the slope of the normoxic CO2 resp onse curve, and a decrease of the extrapolated arterial P-CO2 at zero ventilation. 4. Inhibition of CNS carbonic anhydrase by methazolamide results in an increase in slope and x-intercept of the ventilatory CO2 response curve. 5. Using a mass balance equation for CO2 of a brain c ompartment, it is argued that inhibition of erythrocyte carbonic anhyd rase results in a decrease in slope of the in vivo CO2 dissociation cu rve, which can explain the effects of benzolamide. 6. The changes in s lope and intercept induced by methazolamide are discussed in relation to effects on neurones containing carbonic anhydrase, which may includ e central chemoreceptors.