Effect of acetazolamide and amiloride against sodium metabisulphite-induced bronchoconstriction in mild asthma.
BACKGROUND
Inhaled frusemide but not bumetanide, another loop diuretic, reduces bronchial responsiveness to sodium metabisulphite (MBS). To investigate whether the effect of frusemide could be mediated through mechanisms other than Na+/K+/Cl- cotransporter inhibition, the effects of amiloride--an inhibitor of sodium channels in the airway epithelium--and of acetazolamide--a specific inhibitor of carbonic anhydrase--against MBS challenge were studied.


METHODS
In two separate randomised double blind placebo controlled studies, 10 subjects with mild asthma attended on four separate occasions to inhale 7.5 mg amiloride or matched placebo, and 500 mg acetazolamide or placebo, immediately before MBS challenge. The concentration of MBS required to cause a 20% fall in baseline FEV1 (PC20) was measured.


RESULTS
Amiloride and acetazolamide had no effect on baseline FEV1. Amiloride had no effect against MBS challenge, but acetazolamide increased -log PC20 from a mean (SE) of 0.75 (0.09) to 0.98 (0.06) representing a 0.77 (0.24) doubling dose increase.


CONCLUSIONS
These results suggest that carbonic anhydrase activity in the airways, but not sodium flux, modulates bronchial responsiveness to MBS challenge. The action of frusemide is not likely to involve inhibition of carbonic anhydrase activity.
O'Connor
B J
BJ
Department of Thoracic Medicine, National Heart and Lung Institute, Royal Brompton Hospital, London, UK.
Yeo
C T
CT
Chen-Worsdell
Y M
YM
Barnes
P J
PJ
Chung
K F
KF
D000086:Acetazolamide / Q000494:pharmacology*; D000328:Adult; D000584:Amiloride / Q000494:pharmacology*; D001249:Asthma / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D002256:Carbonic Anhydrases / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012964:Sodium / Q000502:physiology; D013447:Sulfites / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D013447:Sulfites; C005200:sodium metabisulfite; D000584:Amiloride; D012964:Sodium; D002256:Carbonic Anhydrases; D000086:Acetazolamide