The Effect of Low-dose Acetazolamide on the Ventilatory CO2 Response Curve in the Anaesthetized Cat

1. The effect of 4 mg kg-1 acetazolamide (I.V.) on the slope (S) and intercept on the Pa,CO2 axis (B) of the ventilatory CO2 response curve of anaesthetized cats with intact or denervated carotid bodies was studied using the technique of dynamic end-tidal forcing. 2. This dose did not induce an arterial-to-end-tidal PCO2 (P(a-ET),CO2) gradient, indicating that erythrocytic carbonic anhydrase was not completely inhibited. Within the first 2 h after administration, this small dose caused only a slight decrease in mean standard bicarbonate of 1.8 and 1.7 mmol l-1 in intact (n = 7) and denervated animals (n = 7), respectively. Doses of acetazolamide larger than 4 mg kg-1 (up to 32 mg kg-1) caused a significant increase in the P(a-ET),CO2 gradient. 3. In carotid body-denervated cats, 4 mg kg-1 acetazolamide caused a decrease in the CO2 sensitivity of the central chemoreflex loop (Sc) from 1.52 +/- 0.42 to 0.96 +/- 0.32 l min-1 kPa-1 (mean +/- S.D.) while the intercept on the Pa,CO2 axis (B) decreased from 4.5 +/- 0.5 to 4.2 +/- 0.7 kPa. 4. In carotid body-intact animals, 4 mg kg-1 acetazolamide caused a decrease in the CO2 sensitivity of the peripheral chemoreflex loop (Sp) from 0.28 +/- 0.18 to 0.19 +/- 0.12 l min-1 kPa-1. Se and B decreased from 1.52 +/- 0.55 to 0.84 +/- 0.21 l min-1 kPa-1, and from 4.0 +/- 0.5 to 3.0 +/- 0.6 kPa, respectively, not significantly different from the changes encountered in the denervated animals. 5. It is argued that the effect of acetazolamide on the CO2 sensitivity of the peripheral chemoreflex loop in intact cats may be caused by a direct effect on the carotid bodies. Both in intact and in denervated animals the effects of the drug on Sc and B may not be due to a direct action on the central nervous system, but rather to an effect on cerebral vessels resulting in an altered relationship between brain blood flow and brain tissue PCO2.