Low-dose acetazolamide reduces CO(2)-O(2) stimulus interaction within the peripheral chemoreceptors in the anaesthetised cat.

Abstract

1. Using the technique of end-tidal CO(2) forcing, we measured the effect of the carbonic anhydrase inhibitor acetazolamide (4 mg kg(-1), I.V.) on the CO(2) sensitivities of the peripheral and central chemoreflex loops both during hyperoxia and hypoxia in 10 cats anaesthetised with alpha-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 CO(2) 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 CO(2)-O(2) 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 CO(2) 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 CO(2)-O(2) 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.