Related Experiment Videos
Effect of acetazolamide and amiloride against sodium metabisulphite-induced bronchoconstriction in mild asthma
B J O'Connor1, C T Yeo, Y M Chen-Worsdell
1Department of Thoracic Medicine, National Heart and Lung Institute, Royal Brompton Hospital, London, UK.
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.
Insights
Carbonic anhydrase activity in airways, not sodium flux, influences bronchial responsiveness to sodium metabisulphite (MBS). Frusemide's action likely doesn't involve carbonic anhydrase inhibition.
Area of Science:
- Pulmonary Medicine
- Respiratory Physiology
- Pharmacology
Background:
- Inhaled frusemide, a loop diuretic, reduces bronchial responsiveness to sodium metabisulphite (MBS), unlike bumetanide.
- Investigated mechanisms beyond Na+/K+/Cl- cotransporter inhibition for frusemide's effect.
- Examined amiloride (sodium channel inhibitor) and acetazolamide (carbonic anhydrase inhibitor) effects on MBS challenge.
Purpose of the Study:
- To determine if airway carbonic anhydrase activity or sodium flux modulates bronchial responsiveness to MBS.
- To elucidate the mechanism of action for inhaled frusemide in asthma.
Main Methods:
- Two randomized, double-blind, placebo-controlled studies were conducted.
- 10 mild asthma subjects inhaled amiloride or placebo, and acetazolamide or placebo before MBS challenge.
- Bronchial responsiveness was assessed by measuring the concentration of MBS causing a 20% fall in FEV1 (PC20).
Main Results:
- Neither amiloride nor acetazolamide affected baseline FEV1.
- Amiloride showed no effect against MBS challenge.
- Acetazolamide significantly increased bronchial responsiveness to MBS, indicating a protective effect.
Conclusions:
- Airway carbonic anhydrase activity, not sodium flux, modulates bronchial responsiveness to MBS.
- Frusemide's therapeutic effect in asthma is unlikely to be mediated by carbonic anhydrase inhibition.