THE EFFECT OF LOW-DOSE ACETAZOLAMIDE ON THE VENTILATORY CO2 RESPONSE CURVE IN THE ANESTHETIZED CAT

1. The effect of 4 mg kg(-1) acetazolamide (I.V.) on the slope (S) and intercept on the P-a,P-CO2 axis (B) of the ventilatory CO2 response c urve of anaesthetized cats with intact or denervated carotid bodies ma s studied using the technique of dynamic end-tidal forcing. 2. This do se did not induce an arterial-to-end-tidal P-CO2 (P-(a-ET,CO2)) gradie nt, 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), resp ectively. 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 d ecrease in the CO2 sensitivity of the central chemoreflex loop (S-c) f rom 1.52 +/- 0.42 to 0.96 +/- 0.32 l min(-1) kPa(-1) (mean +/- S.D.) w hile the intercept on the P-a,P-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) a cetazolamide caused a decrease in the CO2 sensitivity of the periphera l chemoreflex loop (S-p) from 0.28 +/- 0.18 to 0.19 +/- 0.121 min(-1) kPa(-1). S-c 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, n ot significantly different from the changes encountered in the denerva ted animals. 5. It is argued that the effect of acetazolamide on the C O2 sensitivity of the peripheral chemoreflex loop in intact cats may b e caused by a direct effect on the carotid bodies. Both in intact and in denervated animals the effects of the drug on S-c 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 betwe en brain blood flow and brain tissue P-CO2.