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.