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Cardiovascular effects of SCA40, a novel potassium channel opener, in rats
Author(s) -
Michel A.,
Laurent F.,
Bompart J.,
HadjKaddour K.,
Chapat J.P.,
Boucard M.,
Bonnet P.A.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13917.x
Subject(s) - cromakalim , glibenclamide , propranolol , potassium channel , atropine , in vivo , potassium channel opener , chemistry , tetraethylammonium , potassium channel blocker , pharmacology , thoracic aorta , aorta , heart rate , potassium , muscle relaxation , medicine , muscle contraction , endocrinology , vasodilation , blood pressure , biology , microbiology and biotechnology , organic chemistry , diabetes mellitus
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 μ m ) caused a complete and concentration‐dependent relaxation of rat isolated thoracic aorta contracted with 20 m m KCl but failed to inhibit completely the spasmogenic effects of 80 m m KCl. 3 The ATP‐sensitive K + ‐channel blocker, glibenclamide (3 μ m ), failed to antagonize the relaxant action of SCA40 on 20 m m KCl‐contracted rat isolated thoracic aorta. 4 SCA40 (0.001–100 μ m ) 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 μ m ) 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, N G ‐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.