Am. J. Respir. Crit. Care Med., Vol 152, No. 4, 10 1995, 1164-1169.
Effect of diuretics on allergen-induced contractions of passively sensitized human bronchi in vitro
I Pavord, E Holland, D Baldwin, A Tattersfield and A Knox
Respiratory Medicine Unit, City Hospital, Nottingham, United Kingdom.
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)
