Effect of furosemide on hyperpnea-induced airway obstruction, injury, and microvascular leakage.
Furosemide attenuates hyperpnea-induced airway obstruction (HIAO) in asthmatic subjects via unknown mechanism(s). We studied the effect of furosemide on dry air-induced bronchoconstriction, mucosal injury, and bronchovascular hyperpermeability in a canine model of exercise-induced asthma. Peripheral airway resistance (Rp) was recorded before and after a 2-min dry-air challenge (DAC) at 2,000 ml/min. After pretreatment with aerosolized saline containing 0.75% dimethyl sulfoxide, DAC increased Rp 72 +/- 11% (SE, n = 7) above baseline; aerosolized furosemide (10(-3) M) reduced this response by approximately 50 +/- 6% (P < 0.01). To assess bronchovascular permeability, colloidal carbon was injected (1 ml/kg i.v.) 1 min before DAC, and after 1 h, the vehicle- and furosemide-treated airways were prepared for morphometric analysis. Light microscopy confirmed previous studies showing that DAC damaged the airway epithelium and enhanced bronchovascular permeability. Furosemide did not inhibit dry air-induced mucosal injury or bronchovascular hyperpermeability and in fact tended to increase airway damage and vascular leakage. This positive trend toward enhanced bronchovascular permeability in DAC canine peripheral airways is consistent with the hypothesis that furosemide inhibits HIAO in part by enhancing microvascular leakage and thus counterbalancing the evaporative water loss that occurs during hyperpnea.
Freed
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Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland 21205, USA. afreed@phnet.sph.jhu.edu
Taskar
V
V
Schofield
B
B
Omori
C
C
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D016084:Bronchoconstriction / Q000187:drug effects*; D004195:Disease Models, Animal; D004285:Dogs; D005665:Furosemide / Q000494:pharmacology*; D008297:Male; D012137:Respiratory System / Q000187:drug effects
D005665:Furosemide