Cardiovascular effects of SCA40, a novel potassium channel opener, in rats

1 Experiments have been performed to investigate the cardiovascular actions 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 vitro. 2 SCA40 (0.01–30 μm) caused a complete and concentration‐dependent 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 μm), failed to antagonize the relaxant action of SCA40 on 20 mm KCl‐contracted rat isolated thoracic aorta. 4 SCA40 (0.001–100 μm) had dual effects on rat isolated atria. At low concentrations, SCA40 produced a concentration‐dependent decrease in the rate and force of contractions. At higher concentrations (greater than 1 μm) SCA40 induced concentration‐dependent increases of atrial rate and force. 5 In vivo, in normotensive Wistar rats, SCA40 elicited a dose‐dependent (1–100 μg kg−1) decrease in mean arterial pressure which was accompanied by a moderate dose‐dependent increase in heart rate. SCA40 (100 μg kg−1) had a slightly greater hypotensive effect than cromakalim (100 μg kg−1) but the duration of the hypotension was longer with cromakalim than with SCA40. 6 The hypotensive effect of SCA40 was not reduced by propranolol, atropine, NG‐nitro‐l‐arginine methyl ester (l‐NAME) or glibenclamide. 7 It is concluded that the mechanism by which SCA40 relaxes vascular smooth muscle in vitro and in vivo involves activation of K+‐channels distinct from glibenclamide‐sensitive ATP‐sensitive K+‐channels.