Bradycardic effect of alinidine on in situ and on isolated, blood-perfused heart preparations of dogs.
The cardiovascular effects of alinidine were studied on the donor dog and on the isolated dog right atrial or left ventricular preparation which was cross-perfused with arterial blood from the donor dog. When heart rate and systemic arterial blood pressure of the donor dog were decreased dose-dependently by i.v. administration of alinidine (10-300 micrograms/kg), decreases in atrial rate and atrial developed tension of the isolated preparation were induced in a dose-dependent manner, confirming that i.v. administration of alinidine directly induced negative chronotropic and inotropic effects in situ dog heart. The negative chronotropic effects at lower doses of alinidine were more prominent than the decrease in blood pressure of the anesthetized dog and the negative inotropic effect of the isolated atrium, respectively. Direct injection of alinidine (1-300 micrograms) into the sinus node artery of the isolated atrium induced predominant negative chronotropic responses at lower doses. In paced left ventricular muscle preparations, alinidine reduced the developed tension at higher doses. Ratios (decreases in atrial developed tension per decreases in atrial rate) for alinidine ranged from 1.2 to 2.1, which were smaller than those of acetylcholine, adenosine and verapamil, suggesting that alinidine has a predominant bradycardic property and induces bradycardia due to a different mechanism from those of other bradycardic agents in the isolated and blood-perfused dog heart. The responses to isoproterenol and norepinephrine were suppressed significantly by treatment with alinidine (300 micrograms) predominantly on chronotropism. The alinidine-induced decreases in atrial rate were relatively greater when the rate had been augmented by dibutyryl cyclic AMP and norepinephrine infusion, but the relative depression of contractility was slight. From these results, it is suggested that alinidine attenuates the positive chronotropic effects induced by increases in cyclic AMP without decreasing the positive inotropic ones in the blood-perfused dog atrium.
Ogiwara
Y
Y
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Furukawa
Y
Y
Saegusa
K
K
Takeda
M
M
Chiba
S
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002395:Catecholamines / Q000494:pharmacology; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects
D002317:Cardiovascular Agents; D002395:Catecholamines; D003994:Bucladesine; C022192:alinidine; D003000:Clonidine