A bradycardic agent, UL-FS 49, increases atrial force and decreases ventricular force in isolated, perfused heart preparations of dogs.
We investigated the effects of a bradycardic agent, UL-FS 49 (1,3,4,5-tetrahydro-7,8-dimethoxy-3[3-[[2-(3,4-dimethoxyphenyl) ethyl]methylimino]propyl]-2H-3-benzazepin-2-on hydrochloride), on the sinus rate and atrial contractile force and the ventricular force in the isolated, blood-perfused right atrial and left ventricular preparations of the dog and the inhibition by UL-FS 49 of the negative cardiac responses to acetylcholine, adenosine and cromakalim. UL-FS 49 (0.003-3 mumol) decreased sinus rate, increased atrial force and decreased ventricular force in a dose-dependent manner. The threshold doses of UL-FS 49 (0.03 mumol) for atrial responses were smaller than that (1 mumol) for a ventricular response. The duration of bradycardia induced by UL-FS 49 was longer than the intropic one. Propranolol and atropine did not block the positive inotropic and negative chronotropic responses to UL-FS 49, respectively, in isolated atria. UL-FS 49 (0.1-3 mumol) dose-dependently inhibited the negative chronotropic and inotropic responses to parasympathetic nerve stimulation and acetylcholine exogenously administered. UL-FS 49 at higher doses (1 and 3 mumol) attenuated the negative inotropic but not chronotropic responses to adenosine and cromakalim.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Y
Y
Furukawa
S
S
Takayama
S
S
Sawaki
Y
Y
Inoue
S
S
Chiba
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function; D001552:Benzazepines / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D019806:Cromakalim; D004285:Dogs; D006325:Heart Atria / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D010477:Perfusion; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology; D016276:Ventricular Function
D001552:Benzazepines; D001578:Benzopyrans; D002317:Cardiovascular Agents; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D000241:Adenosine; D000109:Acetylcholine; C043636:zatebradine