Potentiation by dopexamine of the cardiac responses to circulating and neuronally released norepinephrine: a possible mechanism for the therapeutic effects of the drug.
Dopexamine is a new dopamine receptor agonist which also inhibits the uptake of norepinephrine (NE) into sympathetic nerves. Dopexamine was infused intravenously (i.v.) in anesthetized dogs at a rate used for treatment of congestive heart failure (4 micrograms/kg/min) before and during i.v. infusions of NE (0.26 +/- 0.06 and 0.57 +/- 0.12 micrograms/kg/min) and before and during cardioaccelerator nerve stimulation (0.25 and 0.50 Hz). Increments in cardiac contractile force produced by both infusion rates of NE were greater during dopexamine infusion; increases in heart rate (HR) and mean arterial pressure (MAP) produced by the higher infusion of NE also were increased by dopexamine. During cardioaccelerator nerve stimulation, 0.25 and 0.50 Hz, the increments in HR were significantly greater during dopexamine infusion; MAP also increased significantly during cardioaccelerator nerve stimulation (0.50 Hz) in the presence of dopexamine. Plasma NE concentration was significantly elevated during infusion of dopexamine. However, dopexamine did not enhance the elevated plasma NE concentration produced by NE infusions. This study demonstrates that infusion of dopexamine potentiates the cardiovascular effects resulting from neuronally released and exogenously infused NE.
Bass
A S
AS
Department of Pharmacological, University of Chicago, Illinois 60637.
Murphy
M B
MB
Kohli
J D
JD
Goldberg
L I
LI
D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation*; D006333:Heart Failure / Q000188:drug therapy; D007262:Infusions, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000502:physiology*
D000322:Adrenergic Agonists; D014179:Neurotransmitter Uptake Inhibitors; C046318:dopexamine; D004298:Dopamine; D009638:Norepinephrine