Different effects of inhaled amiloride and frusemide on airway responsiveness to dry air challenge in asthmatic subjects

Amiloride, a Na+ channel blocker, and frusemide, an inhibitor of the Na+/K+/2Cl- co-transporter on the basolateral surface of airway epithelial cells, have the potential to affect water transport across the airway epithelium. As isocapnic hyperventilation challenge (ISH) with dry air may provoke airway narrowing in asthmatic subjects by dehydrating the airways, inhaled amiloride and frusemide may reduce airway responsiveness by effecting airway hydration. Fifteen asthmatic subjects (6 females, 9 males), who had a fall in forced expiratory volume in one second (FEV1) of 20% after ISH, inhaled amiloride (11 mg), or its vehicle, from a Fisoneb ultrasonic nebulizer, within 10 min before ISH. On a separate day, eight of these subjects inhaled frusemide (38 mg), from the same Fisoneb, 10 min before ISH. After breathing, 30 l at resting ventilation, subjects breathed at 30% of their maximum voluntary ventilation (MVV i.e. predicted FEV1x35), then at 60% MVV, and finally at MVV for 3 or 4 min. FEV1 was measured 1, 3, 5, 7 and 9 min after each period, or until it was stable. Airway sensitivity was expressed as the ventilation (l-min-1) which provoked a 10, 15, 20 or 30% fall in FEV1, (PVE10, PVE15, PVE20 and PVE30, respectively). There was no significant difference in the PVE10,15,20,30 between the vehicle and amiloride treatment day; however, in the 8 subjects who inhaled frusemide, frusemide caused a significant increase in the PVE20 when compared to amiloride. In conclusion, inhaled amiloride failed to protect against ISH, whereas frusemide was effective at reducing airway responsiveness. Further studies are needed to explain the mechanism of action of frusemide.

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