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Vascular endothelium and Ca2+ antagonists
1Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota 55905.
Journal of Cardiovascular Pharmacology
|January 1, 1988
Summary
Endothelium-dependent relaxing factor release requires increased endothelial cell calcium, but not via voltage-operated calcium channels for acetylcholine-induced responses. Calcium antagonists primarily affect vascular smooth muscle in endothelium-dependent contractions.
Area of Science:
- Vascular Biology
- Endothelial Function
- Pharmacology
Background:
- Endothelial cells produce both relaxing and contracting factors.
- Endothelium-dependent relaxing factor (EDRF) release is calcium-dependent.
Purpose of the Study:
- To investigate the role of calcium channels in endothelium-dependent relaxing factor release.
- To determine the mechanism of action of calcium antagonists on endothelium-dependent contractions.
Main Methods:
- Experiments using Ca2+-free solutions and ionophore A 23187 to assess EDRF release.
- Testing Ca2+-channel agonists, dihydropyridines, verapamil, and diltiazem on EDRF release.
- Evaluating the effects of Ca2+ antagonists (e.g., nisoldipine) on vascular smooth muscle contractions and endothelium-dependent responses.
Main Results:
- EDRF release requires increased endothelial cell cytoplasmic Ca2+ but is not mediated by voltage-operated Ca2+ channels for acetylcholine-induced responses.
- Diltiazem inhibits EDRF release through a non-Ca2+ channel mechanism.
- Ca2+ antagonists synergize with EDRF to inhibit vascular smooth muscle contractions and inhibit endothelium-dependent contractions at the smooth muscle level.
Conclusions:
- Acetylcholine-induced EDRF release involves Ca2+ influx independent of classical voltage-operated channels.
- Calcium antagonists primarily target vascular smooth muscle, not the endothelium, to inhibit endothelium-dependent contractions.