Influence of AQ-A39, a bradycardic agent, on cardiovascular responses to isoproterenol in the anesthetized dog.
The effects of AQ-A39, a selective bradycardic agent, on cardiovascular responses to beta-adrenergic stimulation with isoproterenol were investigated in open-chest, anesthetized dogs. Verapamil and timolol were also studied and compared with AQ-A39. All three compounds decreased basal heart rate and significantly decreased the chronotropic potency of isoproterenol. At 1.0 and 3.0 mg/kg, AQ-A39 reduced the relative potency of isoproterenol on heart rate to 0.730 and 0.312, respectively (control potency = 1.0). AQ-A39 enhanced the isoproterenol-mediated increases in cardiac output without affecting the potency of isoproterenol on mean arterial blood pressure or left ventricular dP/dtmax. Timolol reduced the potency of isoproterenol on all parameters studied. Verapamil decreased the left ventricular dP/dtmax response but did not change the mean arterial blood pressure or cardiac output responses to isoproterenol. Therefore, AQ-A39 demonstrated greater selectivity for inhibiting the chronotropic responses to beta-adrenergic stimulation in vivo than verapamil or timolol. Selective inhibition of positive chronotropic but not positive inotropic responses, as observed with AQ-A39, could be beneficial in the treatment of ischemic heart disease.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D054833:Isoindoles; D007545:Isoproterenol / Q000008:administration & dosage*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010797:Phthalimides / Q000008:administration & dosage*; D013999:Timolol / Q000008:administration & dosage; D014700:Verapamil / Q000008:administration & dosage
D054833:Isoindoles; D010797:Phthalimides; D013999:Timolol; D014700:Verapamil; D007545:Isoproterenol; C030532:falipamil