Cardiovascular effects of the new positive inotropic agent denopamine with special reference to species difference and the effect on failing heart.
Cardiovascular effects of (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol (denopamine, TA-064) were investigated in various experimental animals. An intravenous bolus injection of denopamine dose-dependently increased the contractile force or the maximum rate of rise of left ventricular pressure (LV dp/dtmax in cynomolgus monkeys, miniature pigs, cats and rats. In these animals, the doses of denopamine which increased the contractile force by 30% of the control (ED30) were found to be 2-3 micrograms/kg. On the other hand, ED30 values for dl-isoprenaline ranged from 0.005 to 0.04 micrograms/kg. Thus, the potency of denopamine for increasing the contractility was approximately 1/60-1/300 that of dl-isoprenaline. It is noteworthy that the positive inotropic effect of denopamine was more pronounced than the positive chronotropic effect compared with those of isoprenaline, as estimated at ED30 for positive inotropy. In general, denopamine produced little effect on the blood pressure, and only a slight increase or an increasing tendency was observed in all of these animals. An intravenous continuous infusion of denopamine to monkeys or pigs produced qualitatively similar cardiovascular effects to those following intravenous bolus injection. When examined with monkeys, the positive inotropic effect and plasma levels of denopamine were closely related. Denopamine increased cardiac output, and reduced total peripheral resistance in pigs and dogs. In dogs, common carotid, superior mesenteric and femoral arterial blood flow were increased concomitant with the increase in cardiac output, while the vascular resistance of the corresponding vascular bed was reduced. Denopamine had no significant influence on central venous pressure in monkeys and pulmonary arterial pressure in dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002036:Bundle of His / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002415:Cats; D004562:Electrocardiography; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008252:Macaca fascicularis; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013552:Swine; D013556:Swine, Miniature
D002316:Cardiotonic Agents; D004983:Ethanolamines; C037293:denopamine