Subdiuretic dose of furosemide enhances albuterol effects in asthmatic mice rather than bumetanide

Abstract Background One of the loop diuretics, furosemide, was found useful in bronchial asthma. It enhanced anti-asthmatic effects of albuterol. The underlying mechanism is still unclear. Objective This study was planned to investigate whether the enhancing effect of furosemide for albuterol in ovalbumin-induced asthmatic BALB/c mice is diuretic-related or not. Methods Two sets of experiments were performed. In the first, effects of inhaled subdiuretic doses of furosemide and bumetanide (another loop diuretic) were compared. Treatments (mg/mL) were given as 15 minute-inhalation before final ovalbumin provocation as follows: albuterol (2.5), furosemide (0.08), bumetanide (0.005), (albuterol + furosemide, 2.5 + 0.08), and (albuterol + bumetanide, 2.5 + 0.005). Airway hyperreactivity (AHR) to inhaled methacholine, levels of IL-6, TNF-α, and differential white blood cells in bronchoalveolar lavage fluid (BALF), and lung histopathology were evaluated. In the second set, effects of oral diuretic doses (mg/kg) of furosemide (10) and bumetanide (0.25) were given before final ovalbumin provocation. Urine volume and asthma parameters were measured. Results Ovalbumin-asthmatic mice showed significant increases in AHR, levels of IL-6, TNF-α, and inflammatory cells in BALF, and lung inflammatory cell infiltration. Inhaled furosemide significantly decreased these changes while inhaled bumetanide failed. Albuterol and albuterol + bumetanide significantly decreased these changes more than furosemide while albuterol + furosemide produced the most significant decreases. Both oral furosemide and bumetanide exerted equivalent diuretic effects but failed to improve asthma. Conclusions Inhaled subdiuretic dose of furosemide enhanced effects of albuterol more in ovalbumin-asthmatic mice rather than bumetanide, while oral diuretic doses of both drugs failed to improve asthma, indicating that this enhancing effect is not diuretic-related.