Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
Skip to main content

Inhaled furosemide has been shown to protect subjects with asthma from bronchoconstriction induced by a wide variety of stimuli, including allergen, but the mechanism of action is controversial. We have used an in vitro model of allergen-induced bronchoconstriction to examine the effects of furosemide and other ion transport inhibitors. Human bronchial rings were passively sensitized by incubation with serum from an atopic donor and were challenged with Dermatophagoides pteronyssinus. Allergen-challenged bronchial rings developed bronchoconstriction which was effectively inhibited by the cysteinyl-leukotriene antagonist ICI 198,615 (10(-7) M) and to a lesser extent by terfenadine (10(-5) M). Assessed over 60 min furosemide 10(-6), 10(-5), and 10(-4) M inhibited contractions by a mean (95% confidence interval [CI]) 7.9% (-23.5, 39.3%, p > 0.05), 44.2% (12.9, 75.2%, p < 0.01), and 86.9% (55.5, 118.3%, p < 0.001) respectively (n = 5). The same concentrations of bumetanide inhibited contractions by 21.5% (-8.4, 51.4%, p > 0.05), 13.6% (-16.3, 43.4%, p > 0.05) and 51.6% (21.7, 81.4%, p < 0.01) respectively (n = 5). The sodium transport inhibitor amiloride and the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) were without effect (both 10(-4) M; n = 4). Furosemide increased PGE2 production by the bronchial rings by 134% (95% CI 53, 259%). Indomethacin (3 x 10(-6) M) blocked the furosemide-induced increase in PGE2 production and reduced the protection afforded by 10(-4) M furosemide against allergen-induced contractions from 67.9% to 34.7% (mean difference 33.2%; 95% CI 9.7, 56.6%; p < 0.01; n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Original publication

DOI

10.1164/ajrccm.152.4.7551365

Type

Journal article

Journal

Am J Respir Crit Care Med

Publication Date

10/1995

Volume

152

Pages

1164 - 1169

Keywords

Allergens, Animals, Bronchi, Bronchoconstriction, Bumetanide, Cyclooxygenase Inhibitors, Dinoprostone, Diuretics, Furosemide, Humans, Immunization, Passive, In Vitro Techniques, Indomethacin, Mites