Effects of dopamine, (+/-)-dobutamine and the (+)- and (-)-enantiomers of dobutamine on cardiac function in pithed rats.
The effects of dopamine, (+/-)-dobutamine (racemic mixture) and the (+)- and (-)-enantiomers of dobutamine on myocardial function were evaluated in pithed rats. Dopamine and (+/-)-dobutamine produced effects on cardiac function in pithed rats that were qualitatively similar to those reported for these compounds in humans. The increase in cardiac output produced by dopamine and (+/-)-dobutamine was due mainly to an increase in stroke volume, with increases in heart rate contributing to a significant but lesser degree. For both dopamine and (+/-)-dobutamine, the increase in stroke volume appears to result from an increase in myocardial contractility as assessed by increases in left ventricular (LV) dp/dt. Dopamine produced a marked increase in mean arterial blood pressure, whereas (+/-)-dobutamine only modestly increased blood pressure. The (-)-enantiomer of dobutamine, which possesses mainly alpha-1 adrenoceptor agonist activity, produced dose-dependent increases in cardiac output, stroke volume, LVdp/dt and mean arterial blood pressure, but did not significantly increase heart rate except at high doses. Thus, the increase in cardiac output produced by (-)-dobutamine was derived almost exclusively from an augmentation in stroke volume resulting from an increase in myocardial contractility. In contrast, (+)-dobutamine, which possesses predominantly beta-1 and beta-2 adrenoceptor agonist activity, elicited only a modest increase in cardiac output which was due both to an increase in heart rate and stroke volume. Mean arterial blood pressure was not significantly affected by (+)-dobutamine.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003655:Decerebrate State; D004280:Dobutamine / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D013237:Stereoisomerism
D011942:Receptors, Adrenergic, alpha; D004280:Dobutamine; D004298:Dopamine