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.