EFFECT OF ACETAZOLAMIDE AND AMILORIDE AGAINST SODIUM METABISULFITE-INDUCED BRONCHOCONSTRICTION IN MILD ASTHMA

Background - Inhaled frusemide but not bumetanide, another loop diuret ic, reduces bronchial responsiveness to sodium metabisulphite (MBS). T o investigate whether the effect of frusemide could be mediated throug h mechanisms other than Na+/K+/Cl- cotransporter inhibition, the effec ts of amiloride - an inhibitor of sodium channels in the airway epithe lium - and of acetazolamide - a specific inhibitor of carbonic anhydra se - against MBS challenge were studied. Methods - In two separate ran domised double blind placebo controlled studies, 10 subjects with mild asthma attended on four separate occasions to inhale 7.5mg amiloride or matched placebo, and 500 mg acetazolamide or placebo, immediately b efore MBS challenge. The concentration of MBS required to cause a 20% fall in baseline FEV(1) (PC20) was measured. Results - Amiloride and a cetazolamide had no effect on baseline FEV(1). Amiloride had no effect against MBS challenge, but acetazolamide increased -log PC20 from a m ean (SE) of 0.75 (0.09) to 0.98 (0.06) representing a 0.77 (0.24) doub ling dose increase. Conclusions - These results suggest that carbonic anhydrase activity in the airways, but not sodium flux, modulates bron chial responsiveness to MBS challenge. The action of frusemide is not likely to involve inhibition of carbonic anhydrase activity.