The carbonic anhydrase inhibitors methazolamide and acetazolamide have different effects on the hypoxic ventilatory response in the anaesthetized cat

Abstract

We compared the effects of the carbonic anhydrase inhibitors methazolamide and acetazolamide (3 mg kg(-1), i.v.) on the steady-state hypoxic ventilatory response in 10 anaesthetized cats. In five additional animals, we studied the effect of 3 and 33 mg kg(-1) methazolamide. The steady-state hypoxic ventilatory response was described by the exponential function: *Vi= G exp(-D P(O2)) + A where *Vi is the inspired ventilation, G is hypoxic sensitivity, D is the shape factor and A is hyperoxic ventilation. In the first group of 10 animals, methazolamide did not change parameters G and D, while A increased from 0.86 +/- 0.33 to 1.30 +/- 0.40 l min(-1) (mean +/- s.d., P = 0.003). However, the subsequent administration of acetazolamide reduced G by 44% (control, 1.93 +/- 1.32; acetazolamide, 1.09 +/- 0.92 l min(-1), P = 0.003), while A did not show a further change. Acetazolamide tended to reduce D (control, 0.20 +/- 0.07; acetazolamide, 0.14 +/- 0.06 kPa(-1), P = 0.023). In the second group of five animals, neither low- nor high-dose methazolamide changed parameters G, D and A. The observation that even high-dose methazolamide, causing full inhibition of carbonic anhydrase in all body tissues, did not reduce the hypoxic ventilatory response is reminiscent of previous findings by others showing no change in magnitude of the hypoxic response of the in vitro carotid body by this agent. This suggests that normal carbonic anhydrase activity is not necessary for a normal hypoxic ventilatory response to occur. The mechanism by which acetazolamide reduces the hypoxic ventilatory response needs further study.