Effect of furosemide on hyperpnea-induced airway obstruction, injury, and microvascular leakage

Freed, Arthur N., Varsha Taskar, Brian Schofield, andChiharu Omori. Effect of furosemide on hyperpnea-induced airway obstruction, injury, and microvascular leakage. J. Appl. Physiol. 81(6): 2461-2467, 1996.Furosemideattenuates hyperpnea-induced airway obstruction (HIAO) in asthmaticsubjects via unknown mechanism(s). We studied the effect of furosemideon dry air-induced bronchoconstriction, mucosal injury, andbronchovascular hyperpermeability in a canine model of exercise-inducedasthma. Peripheral airway resistance (Rp) was recorded before and aftera 2-min dry-air challenge (DAC) at 2,000 ml/min. After pretreatmentwith aerosolized saline containing 0.75% dimethyl sulfoxide, DACincreased Rp 72 ± 11% (SE, n = 7) above baseline; aerosolized furosemide(10³ M) reduced thisresponse by ~50 ± 6% (P < 0.01). To assess bronchovascular permeability, colloidal carbon wasinjected (1 ml/kg iv) 1 min before DAC, and after 1 h, the vehicle- andfurosemide-treated airways were prepared for morphometric analysis.Light microscopy confirmed previous studies showing that DAC damagedthe airway epithelium and enhanced bronchovascular permeability.Furosemide did not inhibit dry air-induced mucosal injury orbronchovascular hyperpermeability and in fact tended to increase airwaydamage and vascular leakage. This positive trend toward enhancedbronchovascular permeability in DAC canine peripheral airways isconsistent with the hypothesis that furosemide inhibits HIAO in part byenhancing microvascular leakage and thus counterbalancing theevaporative water loss that occurs during hyperpnea.