CARDIOVASCULAR EFFECTS OF SCA40, A NOVEL POTASSIUM CHANNEL OPENER, INRATS

1 Experiments have been performed to investigate the cardiovascular ac tions in the rat of SCA40, a novel potassium channel opener which is a potent relaxant of guinea-pig airway smooth muscle in vivo and in vit ro. 2 SCA40 (0.01-30 muM) caused a complete and concentration-dependen t relaxation of rat isolated thoracic aorta contracted with 20 mm KCl but failed to inhibit completely the spasmogenic effects of 80 mm KCl. 3 The ATP-sensitive K+-channel blocker, glibenclamide (3 muM), failed to antagonize the relaxant action of SCA40 on 20 mm KCl-contracted ra t isolated thoracic aorta. 4 SCA40 (0.001-100 muM) had dual effects on rat isolated atria. At low concentrations, SCA40 produced a concentra tion-dependent decrease in the rate and force of contractions. At high er concentrations (greater than 1 muM) SCA40 induced concentration-dep endent increases of atrial rate and force. 5 In vivo, in normotensive Wistar rats, SCA40 elicited a dose-dependent (1-100 mug kg-1) decrease in mean arterial pressure which was accompanied by a moderate dose-de pendent increase in heart rate. SCA40 (100 mug kg-1) had a slightly gr eater hypotensive effect than cromakalim (100 mug kg-1) but the durati on of the hypotension was longer with cromakalim than with SCA40. 6 Th e hypotensive effect of SCA40 was not reduced by propranolol, atropine , N(G)-nitro-L-arginine methyl ester (L-NAME) or glibenclamide. 7 It i s concluded that the mechanism by which SCA40 relaxes vascular smooth muscle in vitro and in vivo involves activation of K+-channels distinc t from glibenclamide-sensitive ATP-sensitive K+-channels.