Abstract
Nifedipine, a relatively new Ca2+-channel blocking agent, has recently been shown to be effective in the treatment of exercise-induced asthma; however, the pharmacological mechanism by which it blocks bronchospasm is little understood. We have investigated and characterized its effects on the reactivity of isolated guinea-pig and rat tracheal smooth muscle. Although it (10-8-10-7 M) blocked the contraction of the rat tracheal muscle to KCl and CaCl2, nifedipine (10-7-10-6 M) did not significantly inhibit histamine, methacholine or serotonin-induced muscle contractions in guinea-pigs and the methacholine contraction in rats. Nifedipine produced a potent relaxation on contracted tracheal muscle. The concentration required to produce 50% relaxation of 10-5 M histamine-precontracted guinea-pig tracheal muscle was 8.31 ± 3.12 X 10-9 M, and the extent of the nifedipine-induced relaxation could be modified by the baseline and active contracted tension. Nifedipine was more potent in producing the relaxation in guinea-pig tracheal muscle than isoproterenol, theophylline or verapamil. However, the time required for 50% relaxation by 3 X 10-5 M isoproterenol was significantly less than the time for the nifedipine (3 X 10-5 M) or verapamil (10-4 M) effect. In addition, the Hill number of the nifedipine-induced relaxation was different from the value of the isoproterenol or verapamil effect. Our results indicate that nifedipine exerts a potent dilatory effect directly on airway muscle, and suggest that such effect could be one of its pharmacological actions on relieving bronchospasm.
| Original language | English |
|---|---|
| Pages (from-to) | 228-244 |
| Number of pages | 17 |
| Journal | Archives Internationales de Pharmacodynamie et de Therapie |
| Volume | 263 |
| Issue number | 2 |
| State | Published - 1983 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Pharmacology
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Pharmacological characterization of effects of nifedipine on isolated guinea-pig and rat tracheal smooth muscle. / Cheng, J. B.; Townley, R. G.
In: Archives Internationales de Pharmacodynamie et de Therapie, Vol. 263, No. 2, 1983, p. 228-244.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacological characterization of effects of nifedipine on isolated guinea-pig and rat tracheal smooth muscle
AU - Cheng, J. B.
AU - Townley, R. G.
PY - 1983
Y1 - 1983
N2 - Nifedipine, a relatively new Ca2+-channel blocking agent, has recently been shown to be effective in the treatment of exercise-induced asthma; however, the pharmacological mechanism by which it blocks bronchospasm is little understood. We have investigated and characterized its effects on the reactivity of isolated guinea-pig and rat tracheal smooth muscle. Although it (10-8-10-7 M) blocked the contraction of the rat tracheal muscle to KCl and CaCl2, nifedipine (10-7-10-6 M) did not significantly inhibit histamine, methacholine or serotonin-induced muscle contractions in guinea-pigs and the methacholine contraction in rats. Nifedipine produced a potent relaxation on contracted tracheal muscle. The concentration required to produce 50% relaxation of 10-5 M histamine-precontracted guinea-pig tracheal muscle was 8.31 ± 3.12 X 10-9 M, and the extent of the nifedipine-induced relaxation could be modified by the baseline and active contracted tension. Nifedipine was more potent in producing the relaxation in guinea-pig tracheal muscle than isoproterenol, theophylline or verapamil. However, the time required for 50% relaxation by 3 X 10-5 M isoproterenol was significantly less than the time for the nifedipine (3 X 10-5 M) or verapamil (10-4 M) effect. In addition, the Hill number of the nifedipine-induced relaxation was different from the value of the isoproterenol or verapamil effect. Our results indicate that nifedipine exerts a potent dilatory effect directly on airway muscle, and suggest that such effect could be one of its pharmacological actions on relieving bronchospasm.
AB - Nifedipine, a relatively new Ca2+-channel blocking agent, has recently been shown to be effective in the treatment of exercise-induced asthma; however, the pharmacological mechanism by which it blocks bronchospasm is little understood. We have investigated and characterized its effects on the reactivity of isolated guinea-pig and rat tracheal smooth muscle. Although it (10-8-10-7 M) blocked the contraction of the rat tracheal muscle to KCl and CaCl2, nifedipine (10-7-10-6 M) did not significantly inhibit histamine, methacholine or serotonin-induced muscle contractions in guinea-pigs and the methacholine contraction in rats. Nifedipine produced a potent relaxation on contracted tracheal muscle. The concentration required to produce 50% relaxation of 10-5 M histamine-precontracted guinea-pig tracheal muscle was 8.31 ± 3.12 X 10-9 M, and the extent of the nifedipine-induced relaxation could be modified by the baseline and active contracted tension. Nifedipine was more potent in producing the relaxation in guinea-pig tracheal muscle than isoproterenol, theophylline or verapamil. However, the time required for 50% relaxation by 3 X 10-5 M isoproterenol was significantly less than the time for the nifedipine (3 X 10-5 M) or verapamil (10-4 M) effect. In addition, the Hill number of the nifedipine-induced relaxation was different from the value of the isoproterenol or verapamil effect. Our results indicate that nifedipine exerts a potent dilatory effect directly on airway muscle, and suggest that such effect could be one of its pharmacological actions on relieving bronchospasm.
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M3 - Article
VL - 263
SP - 228
EP - 244
JO - Archives Internationales de Pharmacodynamie et de Therapie
JF - Archives Internationales de Pharmacodynamie et de Therapie
SN - 0003-9780
IS - 2
ER -