Loop diuretics and in vitro relaxation of human fetal and newborn mouse airways

This study was designed to test the hypotheses that furosemide directly causes relaxation in human fetal airway and that delivery of loop diuretics to either the adventitial or epithelial surface of newborn mouse airway results in equivalent relaxation. Isometric tension changes were measured in human fetal (11-16 wk) trachea and mainstem bronchus rings exposed to furosemide (300 microM) or saline after acetylcholine or leukotriene D(4) constriction. Significant decreases in isometric tension to furosemide were demonstrated after constriction with acetylcholine or leukotriene D(4). To examine the site of effect and mimic aerosolized and systemic administration, furosemide (3-300 microM) and bumetanide (0.3-30 microM) were applied separately to epithelial and adventitial surfaces of newborn mouse airways. No differences in airway diameter changes to epithelial or adventitial furosemide or bumetanide were observed, but a 10-fold difference in potency was found. In summary, human fetal airway relaxed to furosemide when constricted with either neurotransmitter or inflammatory mediator in vitro. Further, no differences in relaxation to equimolar epithelial and adventitial furosemide were observed in isolated newborn mouse airway. Taken together, this provides evidence that furosemide has a direct, nonepithelial-dependent effect on airway smooth muscle tone.