Effect of sodium-transport inhibitors on airway smooth muscle contractility in vitro.
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 ethylenediaminetetraacetic 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) mol/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).(ABSTRACT TRUNCATED AT 250 WORDS)
Knox
A J
AJ
Respiratory Medicine Unit, City Hospital, Nottingham, U.K.
Ajao
P
P
Britton
J R
JR
Tattersfield
A E
AE
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014132:Trachea / Q000187:drug effects
D016210:Methacholine Chloride; D010042:Ouabain; D000584:Amiloride; D006632:Histamine; D002217:Carbachol; D000254:Sodium-Potassium-Exchanging ATPase; D009543:Nifedipine; D010646:Phentolamine