Low-dose acetazolamide reduces CO2–O2 stimulus interaction within the peripheral chemoreceptors in the anaesthetised cat

Using the technique of end-tidal CO2 forcing, we measured the effect of the carbonic anhydrase inhibitor acetazolamide (4 mg kg−1, i.v.) on the CO2 sensitivities of the peripheral and central chemoreflex loops both during hyperoxia and hypoxia in 10 cats anaesthetised with α-chloralose–urethane.In the control situation, going from hyperoxia (arterial 47.40 ± 3.62 kPa, mean ± s.d.) into moderate hypoxia ( 8.02 ± 0.30 kPa) led to an almost doubling of the peripheral CO2 sensitivity (SP): a rise from 0.09 ± 0.07 to 0.16 ± 0.06 l min−1 kPa−1. After acetazolamide, however, lowering the from 46.95 ± 5.19 to 8.02 ± 0.66 kPa did not result in a rise in SP, indicating the absence of a CO2–O2 stimulus interaction.In hypoxia, acetazolamide reduced SP from 0.16 ± 0.06 to 0.07 ± 0.05 l min−1 kPa−1. In hyperoxia, however, the effect on SP was much smaller (an insignificant reduction from 0.09 ± 0.07 to 0.06 ± 0.05 l min−1 kPa−1).Acetazolamide reduced both the hyperoxic and hypoxic sensitivities (SC) of the central chemoreflex loop: from 0.45 ± 0.16 to 0.27 ± 0.13 l min−1 kPa−1 and from 0.40 ± 0.16 to 0.26 ± 0.13 l min−1 kPa−1, respectively. In hyperoxia, the apnoeic threshold B (X-intercept of the ventilatory CO2 response curve) decreased from 2.91 ± 0.57 to 0.78 ± 1.9 kPa (P = 0.005). In hypoxia, B decreased from 1.59 ± 1.22 to −0.70 ± 2.99 kPa (P = 0.03).Because acetazolamide abolished the CO2–O2 interaction, i.e. the expected increase in SP when going from hyperoxia into hypoxia, we conclude that the agent has a direct inhibitory effect on the carotid bodies. The exact mechanism by which the agent exerts this effect will remain unclear until more detailed information becomes available on the identity of the carbonic anhydrase iso-enzymes within the carotid bodies and their precise subcellular distribution