Low-dose acetazolamide reduces CO2-O-2 stimulus interaction within the peripheral chemoreceptors in the anaesthetised cat

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 C O2, sensitivities of the peripheral and central chemoreflex loops both duri ng hyperoxia and hypoxia in 10 cats anaesthetised with alpha -chloralose-ur ethane. 2. In the control situation, going from hyperoxia (arterial P-O2(P-a,P-O2)4 7.40 +/- 3.62 kPa, mean +/- S.D.) into moderate hypoxia (P-a,P-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 1 min(-1) kPa(-1). After aceta zolamide, however, lowering the P-a,P-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-O-2 stimulus interaction. 3. In hypoxia, acetazolamide reduced S-p from 0.16 +/- 0.06 to 0.07 +/- 0.0 5 1 min(-1) kPa(-1). In hyperoxia, however, the effect on S-p was much smal ler (an insignificant reduction from 0.09 +/- 0.07 to 0.06 +/- 0.05 1 min(- 1) kPa(-1)). 4. Acetazolamide reduced both the hyperoxic and hypoxic sensitivities (S-p) of the central chemoreflex loop: from 0.45 +/- 0.16 to 0.27 +/- 0.13 1 min (-1) kPa(-1) and from 0.40 +/- 0.16 to 0.26 +/- 0.13 1 min(-1) kPa(-1), res pectively. In hyperoxia, the apnoeic threshold B(X-intercept of the ventila tory CO2 response curve) decreased from 2.91 +/- 0.57 to 0.78 +/- 1.9 kPa ( P = 0.005). fn hypoxia, B decreased from 1.59 +/- 1.22 to -0.70 +/- 2.99 kP a (P = 0.03). 5. Because acetazolamide abolished the CO2-O-2 interaction, i.e. the expect ed increase in S-p when going from hyperoxia into hypoxia, we conclude that the agent has a direct inhibitory effect Oil the carotid bodies. The exact mechanism toy which the agent exerts this effect will remain unclear until more detailed information becomes available on the identity of the carboni c anhydrase iso-enzymes within the carotid bodies and their precise subcell ular distribution.