Effect of dopamine, ibopamine, and epinine on alpha- and beta-adrenoceptors in canine pulmonary circulation.
Dopamine has been widely utilized in the treatment of acute congestive heart failure, ibopamine, the diisobutyrate ester of N-methyldopamine (epinine), is a novel inotropic agent that, unlike-dopamine, is orally active. In clinical studies at doses that produce favorable hemodynamic responses, ibopamine and dopamine can evoke a slight and transient increase in pulmonary artery pressure and pulmonary capillary wedge pressure, an effect that is no longer apparent 1 h after administration. We have previously demonstrated in anesthetized dogs that this effect is due to stimulation of alpha-adrenoceptors in the pulmonary circulation by dopamine and ibopamine, as well as by the active form of ibopamine, epinine. The aim of the present investigation was to determine how dopamine, ibopamine, and epinine interact with beta-adrenoceptors in the canine pulmonary circulation, since this activity may serve to offset the alpha-adrenoceptor-mediated pulmonary vasoconstrictor responses. Intraarterial injection of dopamine, ibopamine, and epinine resulted in dose-dependent pulmonary vasoconstrictor responses with a maximum increase of approximately 50-60% above resting pulmonary vascular tone. When animals were pretreated with propranolol (1 mg/kg iv) to block beta-adrenoceptors, pulmonary vasoconstrictor responses to dopamine were unchanged, whereas pulmonary vasopressor responses to ibopamine and epinine were significantly potentiated, especially for epinine. Upon intraduodenal administration of a therapeutically effective dose of ibopamine (i.e. 36 mg/kg) to normal dogs, virtually no pulmonary pressor response was observed. However, administration of this same dose of ibopamine to dogs pretreated with propranolol (1 mg/kg iv) resulted in a marked pulmonary pressor response. These data indicate that epinine, and therefore the parent compound ibopamine, have the capacity to stimulate beta 2-adrenoceptors in the pulmonary circulation to a far greater degree than dopamine, and that this activity serves to offset, at least in part, the alpha-adrenoceptor-mediated pulmonary vasoconstriction that occurs in response to ibopamine.
Shebuski
R J
RJ
Department of Pharmacology, Smith Kline and French Laboratories, King of Prussia, PA 19406.
Smith
J M
JM
Ruffolo
R
R
D000818:Animals; D003846:Deoxyepinephrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004285:Dogs; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum; D005260:Female; D066298:In Vitro Techniques; D007441:Intubation, Gastrointestinal; D008297:Male; D010477:Perfusion; D011433:Propranolol / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012132:Respiratory Muscles / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; C023487:ibopamine; D011433:Propranolol; D003846:Deoxyepinephrine; D004298:Dopamine