title: Cardiovascular effects of SCA40, a novel potassium channel opener, in rats.
abstract: 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.
authors.affiliation: Laboratoire de Pharmacodynamie URA CNRS 1111, Faculté de Pharmacie, Montpellier, France.
authors.forename: A
authors.initials: A
authors.lastname: Michel
authors.forename: F
authors.initials: F
authors.lastname: Laurent
authors.forename: J
authors.initials: J
authors.lastname: Bompart
authors.forename: K
authors.initials: K
authors.lastname: Hadj-Kaddour
authors.forename: J P
authors.initials: JP
authors.lastname: Chapat
authors.forename: M
authors.initials: M
authors.lastname: Boucard
authors.forename: P A
authors.initials: PA
authors.lastname: Bonnet
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D002319:Cardiovascular System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; D007093:Imidazoles; D010276:Parasympatholytics; D015221:Potassium Channels; D011719:Pyrazines; C080660:6-bromo-8-methylaminoimidazo(1,2-a)pyrazine-2-carbonitrile; D011433:Propranolol; D007545:Isoproterenol