Chronotropic and inotropic effects of terikalant on isolated, blood-perfused atrial and ventricular preparations of dogs.
We investigated the effects of terikalant, which blocks inward rectifier K+ current, on the sinus rate, atrial and ventricular contractile force in the isolated, blood-perfused right atrial and left ventricular preparations of dogs, and the effects of terikalant on the negative cardiac responses to acetylcholine, adenosine or pinacidil (an ATP-sensitive K+ channel opener) and on the positive cardiac responses to norepinephrine. Terikalant (1-100 nmol) decreased sinus rate and briefly and slightly increased atrial contractile force in isolated atria. However, terikalant did not increase ventricular contractile force in isolated ventricles. Neither propranolol nor atropine inhibited the positive inotropic and negative chronotropic responses to terikalant, respectively. Terikalant (10 or 30 nmol) did not significantly affect the negative cardiac responses to acetylcholine, adenosine nor pinacidil and the positive responses to norepinephrine. These results suggest that terikalant decreases sinus rate with a small changes in myocardial contractile force and does not affect the cardiac responses to muscarinic and adenosine receptor agonists, ATP-sensitive K+ channel openers nor beta-adrenoceptor agonists in the dog heart.
Lakhe
M
M
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Furukawa
Y
Y
Yonezawa
T
T
Nagashima
Y
Y
Chiba
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D016275:Atrial Function / Q000187:drug effects*; D001285:Atropine / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology*; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D020110:Pinacidil; D010880:Piperidines / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists; D011433:Propranolol / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D016276:Ventricular Function / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000889:Anti-Arrhythmia Agents; D002839:Chromans; D006146:Guanidines; D010880:Piperidines; D015221:Potassium Channels; D014665:Vasodilator Agents; D020110:Pinacidil; D001285:Atropine; D011433:Propranolol; C063899:terikalant; D000241:Adenosine; D000109:Acetylcholine; D009638:Norepinephrine