Effect of sodium-transport inhibitors on airway smooth muscle contractility in vitro
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A J Knox1, P Ajao, J R Britton
1Respiratory Medicine Unit, City Hospital, Nottingham, U.K.
Abstract:
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)
Insights
Altering sodium transport in airway smooth muscle with ouabain causes contraction, while amiloride induces relaxation. These findings suggest novel therapeutic targets for airway smooth muscle dysfunction.
Area of Science:
- Physiology
- Pharmacology
- Respiratory Medicine
Background:
- Airway smooth muscle (ASM) contractility is crucial for respiratory function.
- Dysregulation of ASM contractility contributes to airway hyperresponsiveness.
- Membrane sodium transport plays a role in cellular excitability and contractility.
Purpose of the Study:
- To investigate the impact of modulating sodium transport on ASM contractility.
- To determine the effects of ouabain (Na+/K+-adenosine triphosphatase inhibitor) and amiloride on ASM.
- To explore the underlying mechanisms of ouabain- and amiloride-induced ASM responses.
Main Methods:
- Studied contractile responses in isolated bovine trachea and human bronchial rings.
- Administered ouabain and amiloride at various concentrations.
- Utilized calcium-free solutions, nifedipine, and phentolamine to probe mechanisms.
- Assessed effects on resting tone and agonist-induced responsiveness.
Main Results:
- Ouabain induced concentration-dependent contractions in bovine trachea and human bronchial rings.
- Ouabain-induced contractions were partially inhibited by calcium-free conditions and nifedipine, indicating calcium channel involvement.
- Amiloride caused concentration-dependent relaxation of carbachol-preconstricted bovine tracheal strips.
- Neither ouabain nor amiloride significantly altered ASM responsiveness to histamine or methacholine.
Conclusions:
- Alterations in sodium transport can modulate ASM contractility.
- Ouabain-induced contraction involves calcium influx via voltage-dependent channels.
- Amiloride demonstrates a relaxant effect on ASM.
- Targeting sodium transport mechanisms may offer new therapeutic strategies for ASM-related disorders.