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

This study was designed to test the hypotheses that furosemide directly cau ses relaxation in human fetal airway and that delivery of loop diuretics to either the adventitial or epithelial surface of newborn mouse airway resul ts in equivalent relaxation. Isometric tension changes were measured in hum an fetal (11-16 wk) trachea and mainstem bronchus rings exposed to furosemi de (300 muM) or saline after acetylcholine or leukotriene D-4 constriction. Significant decreases in isometric tension to furosemide were demonstrated after constriction with acetylcholine or leukotriene D4. To examine the si te of effect and mimic aerosolized and systemic administration, furosemide (3-300 muM) and bumetanide (0.3-30 muM) were applied separately to epitheli al and adventitial surfaces of newborn mouse airways. No differences in air way diameter changes to epithelial or adventitial furosemide or bumetanide were observed, but a 10-fold difference in potency was found. In summary, h uman fetal airway relaxed to furosemide when constricted with either neurot ransmitter or inflammatory mediator in vitro. Further, no differences in re laxation to equimolar epithelial and adventitial furosemide were observed i n isolated newborn mouse airway. Taken together, this provides evidence tha t furosemide has a direct, nonepithelial-dependent effect on airway smooth muscle tone.