The importance of the alpha-adrenoceptor agonist activity of dobutamine to inotropic selectivity in the anaesthetized cat.
Doses of dobutamine (steady-state infusions) required to increase inotropy (as measured by isovolumic indices of contractility) were lower than those required to produce tachycardia in the anaesthetized cat. When compared to isoprenaline, dobutamine produced less tachycardia for common increases in inotropy and thus demonstrated inotropic selectivity in this model. Dobutamine also produced mild pressor effects which were potentiated by beta-adrenoceptor blockade with propranolol. In efforts to define the role of the partial agonist activity of dobutamine for alpha-adrenoceptors in the production of selective inotropy the effects of dobutamine infusions were observed in cats pretreated with the alpha-adrenoceptor antagonist phentolamine. In phentolamine-treated cats dobutamine did not demonstrate inotropic selectivity and showed a relationship between increased inotropy and tachycardia which was not significantly different from that obtained with isoprenaline. In contrast, phentolamine did not change the relationship between isoprenaline-induced tachycardia and increased inotropy. These data suggest that the agonist activity of dobutamine for alpha-adrenoceptors could be responsible for selective inotropy in the anaesthetized cat probably by baroreceptor-mediated reflex modulation of heart rate and/or possible stimulation of inotropic cardiac alpha-adrenoceptors.
Kenakin
T P
TP
Johnson
S F
SF
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000494:pharmacology*; D002415:Cats; D004280:Dobutamine / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; D011433:Propranolol; D008729:Methoxamine; D007545:Isoproterenol; D010646:Phentolamine