Negative chronotropic and positive inotropic effects of a unique cardioactive agent, N,N'-dicyclopropyl methyl piperazine (bis) hydrochloride (INO 2628), in isolated, blood-perfused dog atria.
The effects of a novel piperazine derivative (INO 2628) on sinus node pacemaker activity and atrial contractile force were investigated in isolated, blood-perfused dog atrium. Injections of INO 2628 (0.03-100 mumol) into the sinus node artery of the isolated atrium induced a dose-dependent decrease in sinus rate and an increase in contractile force. The positive inotropic effects at more than 10 mumol were accompanied by a transient negative inotropism. Propranolol did not affect the positive inotropic response to INO 2628, but it significantly suppressed positive chronotropic and inotropic responses to norepinephrine. Atropine at a dose which completely blocked negative chronotropic and inotropic responses to carbachol, produced a slight but significant depression of INO 2628-induced negative chronotropic responses; inotropic responses were unaffected. These results suggest that INO 2628 induces noncholinergic negative chronotropic and nonadrenergic positive inotropic responses in isolated dog atria.
Furukawa
Y
Y
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Akahane
K
K
Ogiwara
Y
Y
Chiba
S
S
D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000187:drug effects*; D013268:Stimulation, Chemical
D002317:Cardiovascular Agents; D010879:Piperazines; C059182:N,N'-dicyclopropylmethylpiperazine