EFFECT OF SODIUM-TRANSPORT INHIBITORS ON AIRWAY SMOOTH-MUSCLE CONTRACTILITY INVITRO

1. To determine whether alterations in membrane sodium transport in airway smooth muscle can alter its contractility, we studied the effect of ouabain (a Na+/K+-adenosine triphosphatase inhibitor) and amiloride on contractile responses in bovine trachea and human bronchial rings in a series of studies. 2. Ouabain (10-6-10-4 mol/l) caused concentration-related contraction of bovine trachea with a maximum effect at 30 min; the mean increases in tension with 10-6, 10-5 and 10-4 mol/l ouabain were 19, 27, and 32%, respectively, of the maximum response seen with 10-3 mol/l histamine (n = 6). In human bronchial rings, ouabain (10-5 mol/l) caused a mean contraction which was 40% of the maximum response to methacholine (n = 8). 3. Calcium-free fluid (plus ethylenediaminetetra-acetic acid) and nifedipine (10-5 mol/l) inhibited ouabain-induced contractions, suggesting that contraction was mediated in part by calcium entry via voltage-dependent calcium channels. Phentolamine (10-5 ml/l) was without effect. 4. Ouabain (10-5 mol/l) did not alter histamine responsiveness in bovine trachea or methacholine responsiveness in human bronchial rings. 5. Amiloride did not affect resting tone in bovine trachea but caused a concentration-dependent relaxation of bovine tracheal strips preconstricted with carbachol, 10-3 mol/l amiloride relaxing strips completely over 15 minutes (n = 8). Pretreatment with amiloride significantly inhibited contraction produced by both histamine and carbachol in a dose-related manner, 10-5, 10-4 and 10-3 mol/l amiloride shifting the concentration of histamine producing 50% maximal contraction by 3-, 8- and 35-fold (n = 10) and that of carbachol by 1.4-, 6- and 86-fold (n = 8), respectively. 6. Amiloride also reduced the contraction produced by 10-4 mol/l ouabain from 32% (control) to 7% of the maximum histamine response. 7. Our results suggest that alterations in cell membrane sodium transport modify the contractile properties of airway smooth muscle.