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 N a+/K+/2Cl- co-transporter on the basolateral surface of airway epithel ial cells, have the potential to affect water transport across the air way 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 respon siveness by effecting airway hydration. Fifteen asthmatic subjects (6 females, 9 males), who had a fall in forced expiratory volume in one s econd (FEV1) of 20% after ISH, inhaled amiloride (11 mg), or its vehic le, from a Fisoneb(TM) ultrasonic nebulizer, within 10 min before ISH. On a separate day, eight of these subjects inhaled frusemide (38 mg), from the same Fisoneb(TM), 10 min before ISH. After breathing, 30 1 a t resting ventilation, subjects breathed at 30% of their maximum volun tary ventilation (MVV i.e. predicted FEV1x35), then at 60% MVV, and fi nally at MVV for 3 or 4 min. FEV, was measured 1, 3, 5, 7 and 9 min af ter each period, or until it was stable. Airway sensitivity was expres sed as the ventilation (l.min-1) which provoked a 10, 15, 20 or 30% fa ll in FEV1, (PVE10, PVE15, PVE20 and PVE30, respectively). There was n o significant difference in the PVE10,15,20,30 between the vehicle and amiloride treatment day; however, in the 8 subjects who inhaled fruse mide, frusemide caused a significant increase in the PVE20 when compar ed to amiloride. In conclusion, inhaled amiloride failed to protect ag ainst ISH, whereas frusemide was effective at reducing airway responsi veness. Further studies are needed to explain the mechanism of action of frusemide.