Na+ -K+ -2Cl- co-transport inhibition and bronchoprotective effect of inhaled furosemide in asthmatics
W. Barg, J. Liebhart, E. Liebhart, A. Orda, A. Obojski, A. M. Fal, J. Malolepszy (Wroclaw, Poland)
Source: Annual Congress 2002 - Bronchial responsiveness in asthma and COPD
Session: Bronchial responsiveness in asthma and COPD
Session type: Poster Discussion
Number: 1208
Disease area: Airway diseases
Abstract Background: Prenebulisation with furosemide results in bronchoprotection against indirect stimuli. Furosemide inhibits Na+ -K+ -2Cl- co-transport thus one speculates that its bronchoprotective activity might depend on transmembranal ion fluxes repression. Objective: Earlier we demonstrated that furosemide can prevent bronchoconstroction induced by ultrasonically nebulised distilled water (UNDW). The aim of this experiment was to examine if this in vivo ability correlats with Na+ -K+ -2Cl- co-transport activity in vitro. Methods: Fourteen asthmatics aged from 20 to 52 years underwent two UNDW challenges preceded with furosemide or 0,9%NaCl nebulisations in a double-blind, crossover manner, at least 48 hours apart. The UNDW was administrated for 30, 60,120, 240 and 480 seconds and stopped if FEV1 < 80% from baseline. Further we examinated total transmembranel sodium flux and Na+ -K+ -2Cl- co-transport activities in peripheral blood lymphocytes using 22 Na. Furosemide 10–4 mol was used as an inhibitor of the co-transport. For statistical analysis multiple linear regression with stepwise variable selections was used. Results: We demonstrated that the bronchoprotective effect of prenebulization with furosemide (expressed as area under FEV1 curve) was highly correlated with baseline FEV1 and Na+ -K+ -2Cl- co-transport activity (r=0,96, p=0,001), but not with total sodium flux. The effect of furosemide was signifficantly different from that of saline (p= 0,0392). Conclusion: Bronchorotective effect of furosemide against UNDW is at least in part due to Na+ -K+ -2Cl- co-transport inhibiton. To our knowledge this is the first study comparing in vitro and in vivo effects of furosemide in asthmatics.
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W. Barg, J. Liebhart, E. Liebhart, A. Orda, A. Obojski, A. M. Fal, J. Malolepszy (Wroclaw, Poland). Na+ -K+ -2Cl- co-transport inhibition and bronchoprotective effect of inhaled furosemide in asthmatics. Eur Respir J 2002; 20: Suppl. 38, 1208
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