TEA inhibits ACh-induced EDRF release: endothelial Ca(2+)-dependent K+ channels contribute to vascular tone
| Autor: | A. C. Van Breemen, R. E. Laskey, J. Rusko, E. Demirel, David J. Adams |
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| Rok vydání: | 1994 |
| Předmět: |
Agonist
Male Vascular smooth muscle Potassium Channels Physiology medicine.drug_class Stimulation Nitric Oxide Glibenclamide chemistry.chemical_compound Physiology (medical) medicine.artery medicine Potassium Channel Blockers Thoracic aorta Animals Aorta Tetraethylammonium Chemistry Intracellular Membranes Tetraethylammonium Compounds Acetylcholine Vasodilation Vasomotor System Anesthesia cardiovascular system Biophysics Biological Assay Calcium Female Endothelium Vascular Rabbits Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | The American journal of physiology. 267(3 Pt 2) |
| ISSN: | 0002-9513 |
| Popis: | The effects of K(+)-channel blockers on the acetylcholine (ACh)-induced relaxation of vascular smooth muscle, intracellular free Ca2+ concentration ([Ca2+]i) elevation, and ACh-evoked outward K+ current of endothelial cells of rabbit aorta were studied using bioassay, spectrofluorimetry, and patch-clamp techniques, respectively. In bioassay experiments, ACh caused relaxation of endothelium-denuded aortic rings in a concentration-dependent manner when perfused through an endothelium-intact donor segment of aorta but not when perfused directly onto the recipient aortic ring. ACh-induced relaxation was inhibited by perfusion of tetraethylammonium ions (TEA; 5 mM) through the donor but not by perfusion directly onto the recipient segment. Glibenclamide had no effect on ACh-induced relaxation of the bioassay ring in either situation. ACh increased [Ca2+]i at the endothelial surface of aortic strips but not at the adventitial surface. TEA inhibited ACh-induced [Ca2+]i elevation, whereas glibenclamide had no effect. In patch-clamp experiments with freshly isolated endothelial cells, ACh evoked a biphasic outward current which was completely abolished by TEA (3 mM). It is concluded that Ca(2+)-dependent K+ channels are important for increasing [Ca2+]i during agonist stimulation and consequently for the synthesis/release of endothelium-derived relaxing factors (EDRFs). Furthermore, endothelial ATP-sensitive K+ channels do not contribute to ACh-induced relaxation or evoke an increase in endothelial [Ca2+]i of rabbit thoracic aorta. |
| Databáze: | OpenAIRE |
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