Inotropic mechanisms of dopexamine hydrochloride in horses.
Mechanisms responsible for the positive inotropic effects of dopexamine were investigated in 8 halothane-anesthetized horses. The hemodynamic effects of increasing infusions of dopexamine (5, 10, 15 micrograms/kg of body weight/min) were determined before and after sequential administration of specific antagonists. Using glycopyrrolate and chlorisondamine, and atenolol and ICI 118,551, muscarinic and nicotinic ganglionic, and beta 1, and beta 2-adrenergic receptor blockade, respectively, was induced. Dopexamine infusions induced increase in heart rate, cardiac output, systolic and mean arterial blood pressure, and maximal rate of left ventricular pressure development (+dP/dtmax). Right atrial pressure and systemic vascular resistance decreased. Parasympathetic and ganglionic blockade attenuated cardiac output, systolic and mean aortic blood pressures, and +dP/dtmax responses to dopexamine infusion. Dopexamine-induced increase in heart rate was potentiated by parasympathetic and ganglionic blockade. beta 1-Adrenergic receptor blockade decreased heart rate, cardiac output, arterial blood pressure, and +dP/dtmax from baseline values and markedly reduced the response to dopexamine infusion. beta 2-Adrenergic receptor blockade induced further decrease in hemodynamic variables from baseline values and completely abolished the cardiostimulatory effects of dopexamine on +dP/dtmax. These data indicate that baroreflex activity, beta 1- and beta 2-adrenergic receptor stimulation may be an important cause of dopexamine's positive inotropic effects in horses.
Department of Veterinary Clinical Sciences, Ohio State University, Columbus 43210.
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D000322:Adrenergic Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018492:Dopamine Antagonists; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006736:Horses / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology; D013268:Stimulation, Chemical; D014655:Vascular Resistance / Q000187:drug effects
D000322:Adrenergic Agonists; D000319:Adrenergic beta-Antagonists; D018492:Dopamine Antagonists; D011412:Propanolamines; C046318:dopexamine; C026777:ICI 118551; D001262:Atenolol; D004298:Dopamine