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

Abstract

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.

Interaction between ion transporters and the mucociliary transport system in dog and baboon

“…However, for this effect to cause the observed result, furosemide would have to block inhibitory sensory nerves that regulate secretion so that their inhibition thereby stimulates mucociliary transport. A furosemide-induced increase in microvascular leakage (8) is consistent with our observations.…”

Mild dehydration: a risk factor of broncho-pulmonary disorders?

“…Epidemiological studies investigating the role of fluid and salt input in the etiology of asthma have led so far to conflicting results (for a review, see Ardern & Ram, 2001). Furosemide inhalation was shown in part to inhibit hyperpnea-induced airway obstruction (Freed et al, 1996). There are studies indicating impaired water excretion in asthma (Dawson et al, 1984;Singleton et al, 1986), whereas others note a trend towards hypertonicity during acute airway obstruction (Bahna & Kaushik, 1984), followed by weight gain and decrease of hematocrit during recovery (Gopalan et al, 1983).…”

Alternative strategies in the treatment of bronchial asthma

“…Bianco and colleagues were the first to show that nebulized frusemide attenuates exercise‐induced bronchoconstriction [ 246]. Since then the inhibitory effect of nebulized frusemide has been shown in a number of indirect bronchial provocation tests [ 247–256]. In addition, inhaled frusemide might reduce bronchoconstriction during allergen‐induced early‐ and late‐phase reactions [ 257, 258].…”

“…Frusemide has inhibitory effects on histamine release in vitro [ 261], and reduces mediator release from eosinophils in vitro [ 262]. Alternatively, frusemide might counterbalance ion and water movement across airway epithelium [ 246, 253, 260].…”