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

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 mu M) more patently than those induced by K+ (48 mM). In rat aorta, tetraethylammonium (10 mM), charybdotoxin (0.2 mu M), and iberiotoxin (0.1 mu M), but not glibenclamide (10 IJ-M), attenuated the relaxant effects of YC-1. In guinea pig a. carotis, YC-1 (30 mu M) induced a hyperpolarisation which was antagonised by 1H-[1,2,3]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 50 mu M). In rat aorta, YC-1 (30 mu M) increased the rate constant of Rb-86-reflux. The effect of YC-1 was potentiated by zaprinast (10 mu M), but inhibited by ODQ (50 mu M) or charybdotoxin (0.2 mu M). In smooth muscle cells from rat aorta, YC-1 (10 mu M) increased BKCa channel activity. It is suggested that YC-1-induced vasorelaxation is partially mediated by the activation of K+ channels. (C) 1999 Elsevier Science B.V. All rights reserved.