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 microM) 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 microM), failed to antagonize the relaxant action of SCA40 on 20 mM KCl-contracted rat isolated thoracic aorta. 4. SCA40 (0.001-100 microM) 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 microM) SCA40 induced concentration-dependent increases of atrial rate and force. 5. In vivo, in normotensive Wistar rats, SCA40 elicited a dose-dependent (1-100 micrograms kg-1) decrease in mean arterial pressure which was accompanied by a moderate dose-dependent increase in heart rate. SCA40 (100 micrograms kg-1) had a slightly greater hypotensive effect than cromakalim (100 micrograms 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 with SCA40 relaxes vascular smooth muscle in vitro and in vivo involves activation of K(+)-channels distinct from glibenclamide-sensitive ATP-sensitive K(+)-channels.