Cardiovascular effects of 2-amino-N-(2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide dihydrochloride (Ro 22-9194) in the isolated, cross-perfused atrium of the dog.
The cardiovascular effects of 2-amino-N-(2,6-dimethylphenyl)-N-[3- (3-pyridyl)propyl]propionamide dihydrochloride (Ro 22-9194) were investigated in the canine isolated atrial preparation perfused with arterial blood from another donor dog. Intravenous administration of Ro 22-9194 (0.3-3 mg/kg) reduced heart rate and systemic arterial blood pressure of the donor dog. Simultaneously, in the isolated atrium perfused with donor's blood, negative chronotropic and inotropic responses were induced in a dose-dependent manner. Direct administration of Ro 22-9194 (1-300 micrograms) into the sinus node artery of the isolated atrium induced negative chrono- and inotropic responses and a transient increase in coronary blood flow in a dose-related manner. Mexiletine (1-300 micrograms) also induced negative chrono- and inotropic responses. The potency of Ro 22-9194 for negative cardiac effects was similar to that of mexiletine. The negative cardiac effects of Ro 22-9194 were not modified by atropine in doses which significantly inhibited the cardiac effects of acetylcholine. Ro 22-9194 did not affect the cardiac responses to norepinephrine and to acetylcholine significantly. These results suggest that Ro 22-9194 has non-cholinergic cardiac depressant properties with its vasodilating action, and it has neither anti-adrenergic nor anti-cholinergic actions on the dog heart.
Murakami
M
M
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Furukawa
Y
Y
Karasawa
Y
Y
Ren
L M
LM
Chiba
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002319:Cardiovascular System / Q000187:drug effects*; D002909:Chronobiology Phenomena; D003427:Cross Circulation; D004285:Dogs; D006321:Heart / Q000187:drug effects; D006325:Heart Atria; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000187:drug effects
D011725:Pyridines; C066993:Ro 22-9194; D001285:Atropine; D000109:Acetylcholine; D009638:Norepinephrine