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

Luc J. Teppema, Albert Dahan and Cees N. Olievier

1. 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 -chloralose-urethane.
2. In the control situation, going from hyperoxia (arterial P_O2 (P_a,O2) 47.40 ± 3.62 kPa, mean ± S.D.) into moderate hypoxia (P_a,O2 8.02 ± 0.30 kPa) led to an almost doubling of the peripheral CO₂ sensitivity (S_P): a rise from 0.09 ± 0.07 to 0.16 ± 0.06 l min^-1 kPa^-1. After acetazolamide, however, lowering the P_a,O2 from 46.95 ± 5.19 to 8.02 ± 0.66 kPa did not result in a rise in S_P, indicating the absence of a CO₂-O₂ stimulus interaction.
3. In hypoxia, acetazolamide reduced S_P from 0.16 ± 0.06 to 0.07 ± 0.05 l min^-1 kPa^-1. In hyperoxia, however, the effect on S_P was much smaller (an insignificant reduction from 0.09 ± 0.07 to 0.06 ± 0.05 l min^-1 kPa^-1).
4. Acetazolamide reduced both the hyperoxic and hypoxic sensitivities (S_C) 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).
5. Because acetazolamide abolished the CO₂-O₂ interaction, i.e. the expected increase in S_P 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.

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