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Updated: Aug 20, 2026
In vitro Measurements of Tracheal Constriction Using Mice
Published on: June 25, 2012
Mechanism of ouabain-induced contractions in guinea-pig tracheal rings
R Espinosa-Tanguma1, J R Valle-Aguilera, O Zarazúa-Garcia
1Departament of Fisiologia y Farmacologia, Facultad de Medicina, Universidad Autonóma de San Luis Potosí, San Luis Potosí, SLP Mexico.
Abstract:
The aim of the present study was to analyse the mechanism that underlies the force development induced by ouabain (ED(100) = 100 micromol/L) in guinea-pig tracheal rings. The dose-response curve showed that concentrations of ouabain above 100 micromol/L evoked smaller contractions. Ouabain, at 100 micromol/L, produced two long-lasting consecutive transient contractions. The peak of the first contraction was 750 +/- 75 mg, whereas the peak of the second contraction was 280 +/- 46 mg. Both contractions induced by ouabain were dependent on extracellular Ca(2+). Consistent with this, verapamil (10 micromol/L) inhibited the first and second contractions by 77 and 59%, respectively. 3,4-Dichlorobenzamil (20 micromol/L) inhibited the first and second contractions by 68 and 97%, respectively. Simultaneous exposure to 15 mmol/L sodium solution and 100 micromol/L ouabain evoked only one transient contraction, larger (987 +/- 135 mg) than either of the ouabain-induced contractions. Inhibition of the sarcoendoplasmic reticulum Ca-ATPase with cyclopiazonic acid potentiated the first and second ouabain-induced contractions by 47 and 300%, respectively. Atropine (1 micromol/L) inhibited the first and second contractions by 44 and 76%, respectively. In conclusion, the results of the present study are relevant to the understanding of the mechanisms by which ouabain (100 micromol/L) contracts guinea-pig tracheal rings. At the muscular level, oubain induces Ca(2+) influx through L-type Ca(2+) channels and the reverse mode of the sodium-calcium exchanger. At the nerve terminals, ouabain promotes the release of acetylcholine secondary to the increase in Ca(2+) influx mediated by the reverse mode of the sodium-calcium exchanger.
Insights
Ouabain causes guinea-pig tracheal rings to contract by increasing intracellular calcium. This occurs through calcium influx via L-type channels and the sodium-calcium exchanger, and also by releasing acetylcholine.
Area of Science:
- Pharmacology
- Physiology
- Biochemistry
Background:
- Ouabain is a cardiac glycoside known to affect ion transport.
- Its effects on smooth muscle, particularly in the airways, require further elucidation.
- Understanding force development in tracheal smooth muscle is crucial for respiratory research.
Purpose of the Study:
- To analyze the mechanism of force development induced by ouabain in guinea-pig tracheal rings.
- To investigate the role of extracellular calcium and specific ion channels in ouabain-mediated contractions.
- To determine the involvement of the sodium-calcium exchanger and acetylcholine release.
Main Methods:
- Dose-response analysis of ouabain on tracheal ring contractions.
- Assessment of contractions' dependence on extracellular calcium (Ca2+).
- Inhibition studies using verapamil, 3,4-dichlorobenzamil, cyclopiazonic acid, and atropine.
Main Results:
- Ouabain (100 micromol/L) induced two long-lasting contractions dependent on extracellular Ca2+.
- Verapamil and 3,4-dichlorobenzamil partially inhibited these contractions.
- Cyclopiazonic acid potentiated contractions, while atropine inhibited them, suggesting complex mechanisms involving calcium handling and neurotransmission.
Conclusions:
- Ouabain induces tracheal smooth muscle contraction via Ca2+ influx through L-type Ca2+ channels and the reverse mode of the sodium-calcium exchanger.
- Ouabain also promotes acetylcholine release from nerve terminals, contributing to tracheal contraction.
- These findings enhance the understanding of ouabain's pharmacological actions on airway smooth muscle.
