Involvement of K + channels in the relaxant effects of YC-1 in vascular smooth muscle

• Published in: European journal of pharmacology 1999-10, Vol.382 (1), p.11-18
• Main Authors: Seitz, Sabine, Wegener, Jörg W, Rupp, Johanna, Watanabe, Makino, Jost, Andreas, Gerhard, Rolf, Shainberg, Asher, Ochi, Rikuo, Nawrath, Hermann
• Format: Article
• Language: English
• Subjects: Animals; Aorta, Thoracic - drug effects; Biological and medical sciences; BK Ca channel; Blood vessels and receptors; Carotid Arteries - drug effects; Cyclic GMP; Dose-Response Relationship, Drug; Drug Interactions; Female; Fundamental and applied biological sciences. Psychology; Guanylyl cyclase, soluble; Guinea Pigs; In Vitro Techniques; Indazoles - pharmacology; Male; Membrane Potentials - drug effects; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; Phenylephrine - pharmacology; Potassium - physiology; Potassium Channels - physiology; Rats; Rats, Sprague-Dawley; Relaxation; Smooth muscle, vascular; Time Factors; Vasodilation - drug effects; Vertebrates: cardiovascular system
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(99)00574-9

This study addresses the question whether K + channels are involved in the vasorelaxant effects of 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl-indazole (YC-1 ). In rat aorta, guinea pig aorta, and guinea pig a. carotis, YC-1 inhibited contractions induced by phenylephrine (3 μM) more potently than those induced by K +(48 mM). In rat aorta, tetraethylammonium (10 mM), charybdotoxin (0.2 μM), and iberiotoxin (0.1 μM), but not glibenclamide (10 μM), attenuated the relaxant effects of YC-1. In guinea pig a. carotis, YC-1 (30 μM) induced a hyperpolarisation which was antagonised by 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ; 50 μM). In rat aorta, YC-1 (30 μM) increased the rate constant of 86Rb-efflux. The effect of YC-1 was potentiated by zaprinast (10 μM), but inhibited by ODQ (50 μM) or charybdotoxin (0.2 μM). In smooth muscle cells from rat aorta, YC-1 (10 μM) increased BK Ca channel activity. It is suggested that YC-1-induced vasorelaxation is partially mediated by the activation of K + channels.