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Some effects of nifedipine in guinea-pig isolated trachealis
Abstract:
In trachealis depolarized by a K+-rich medium, nifedipine (0.001-1 mumol 1(-1) caused concentration-dependent antagonism of CaCl2-induced increase in tension, moving the CaCl2 log concentration-effect curve to the right and depressing the maximal response. In trachealis in normal Krebs solution, similar concentrations of nifedipine had marked antispasmogenic activity against the responses to potassium chloride (KCl) and tetraethylammonium (TEA). However, nifedipine had little, if any, antispasmogenic activity against the responses to acetylcholine or histamine. Nifedipine 1 mumol 1(-1) was tested for spasmolytic activity in tissues generating tension in response to the EC50 of acetylcholine, KCl or CaCl2. In producing spasmolysis nifedipine was most effective against CaCl2 and least effective against acetylcholine. Nifedipine (0.01-1 mumol-1) had little or no effect on the tone of trachealis in normal Krebs solution. Intracellular electrophysiological recording showed that nifedipine 1 mumol 1(-1) could abolish spontaneous slow wave activity. This was associated with very minor depolarization and little or no loss of mechanical tone. In tissues treated with TEA (8 mmol 1(-1) nifedipine abolished spike and slow wave discharge and reduced mechanical activity to the pre-TEA level. It is concluded that nifedipine prevents KCl- or TEA-induced spasm by inhibition of Ca2+ influx. Spasm evoked by acetylcholine or histamine and the maintenance of spontaneous tone depend largely on mechanisms for increasing the cytoplasmic concentration of free Ca2+ which are resistant to nifedipine.
Insights
Nifedipine effectively blocks muscle spasms caused by calcium (Ca2+) influx, particularly those triggered by potassium chloride (KCl) and tetraethylammonium (TEA). However, it shows limited effect on spasms induced by acetylcholine or histamine, suggesting different underlying mechanisms.
Area of Science:
- Pharmacology
- Physiology
- Smooth Muscle Biology
Background:
- Smooth muscle contraction is regulated by intracellular calcium levels.
- Nifedipine is a calcium channel blocker used clinically.
- Understanding nifedipine's specific mechanisms in different smooth muscle contexts is crucial.
Purpose of the Study:
- To investigate the antispasmogenic and spasmolytic effects of nifedipine on tracheal smooth muscle.
- To elucidate the role of calcium influx in mediating responses to various spasmogens.
- To differentiate nifedipine's actions based on the underlying mechanisms of smooth muscle contraction.
Main Methods:
- Concentration-dependent nifedipine administration in isolated tracheal smooth muscle preparations.
- Measurement of isometric tension in response to various stimuli: CaCl2, KCl, tetraethylammonium (TEA), acetylcholine, and histamine.
- Intracellular electrophysiological recordings to assess membrane potential and electrical activity.
Main Results:
- Nifedipine concentration-dependently antagonized CaCl2-induced contractions and KCl/TEA-induced spasms, indicating inhibition of Ca2+ influx.
- Nifedipine exhibited minimal effect on acetylcholine- or histamine-induced contractions, suggesting nifedipine-resistant calcium signaling pathways.
- Nifedipine abolished spontaneous slow wave activity and TEA-induced spikes, reducing mechanical activity to baseline levels.
Conclusions:
- Nifedipine prevents KCl- and TEA-induced spasms by inhibiting voltage-dependent calcium influx.
- Acetylcholine- and histamine-induced spasms, as well as spontaneous tone, rely on nifedipine-resistant mechanisms for increasing intracellular free Ca2+.
- These findings highlight distinct calcium handling pathways in smooth muscle activation.
