Calcium-Activated Potassium Channels and Nitrate-Induced Vasodilation in Human Coronary Arteries

• Published in: The Journal of pharmacology and experimental therapeutics 1998-04, Vol.285 (1), p.293
• Main Authors: Bychkov, R, Gollasch, M, Steinke, T, Ried, C, Luft, F C, Haller, H
• Format: Article
• Language: English
• Subjects: Coronary Vessels - drug effects; Coronary Vessels - physiology; Heart - drug effects; Heart - physiology; Humans; Hydrazines - pharmacology; Isosorbide Dinitrate - analogs & derivatives; Isosorbide Dinitrate - pharmacology; Mutagens - pharmacology; Myocardial Contraction - drug effects; Nitrates - adverse effects; Nitrates - pharmacology; Nitrogen Oxides; Nitroprusside - pharmacology; Potassium Channels - drug effects; Potassium Channels - metabolism; Vasodilation - drug effects; Vasodilator Agents - pharmacology
• ISSN: 0022-3565; 1521-0103

In some but not all arterial beds, smooth muscle cell calcium-activated K + channels (K Ca channels) play a central role in the mediation of the vasodilator response to nitric oxide (NO) and other nitrates. We investigated the effect of nitrates on K Ca channels in the relaxation of human coronary arteries by means of isometric contraction experiments in arterial rings. We also measured whole-cell currents in freshly isolated human coronary artery vascular smooth muscle cells via the patch-clamp technique. Sodium nitroprusside, diethylamine-nitric oxide complex sodium salt and isosorbide mononitratre completely relaxed rings preconstricted with 5 μM serotonin and produced dose-dependent relaxations of 5 μM serotonin-preconstricted human rings. The relaxations were inhibited by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-oxyl 3-oxide (10 μM), which neutralizes nitric oxide. The K Ca channel blockers iberiotoxin (100 nM) and tetraethylammonium ions (1 mM) significantly inhibited SNP-induced relaxations of human coronary arteries. Moreover, in the patch-clamp experiments, SNP (1 μM) stimulated K Ca currents and spontaneous transient outward K + currents carried by Ca spark activated K Ca channels. The SNP-induced (1 μM) K Ca current was strongly inhibited by iberiotoxin (100 nM). These data show that activation of K Ca channels in smooth muscle cells contributes to the vasodilating actions of nitrates and nitric oxide in human coronary arteries. This finding may have unique clinical significance for the development of antianginal and antihypertensive drugs that selectively target K + channels and Ca sparks..