Suppression of sympathetic ganglionic neurotransmission by the selective dopamine-1 receptor agonist fenoldopam (SK&F 82526) in the anesthetized dog.
This study was designed to determine the role of dopamine (DA) receptors in modulation of sympathetic ganglionic neurotransmission utilizing the selective DA-1 agonist fenoldopam. Preganglionic stimulation of cardiac sympathetic nerves (0.5-2.0 Hz), in pentobarbital anesthetized dogs, resulted in frequency-dependent tachycardia. Fenoldopam (10 and 30 micrograms/kg/min i.v.) suppressed the tachycardic response 45% at 0.5 Hz with no significant effect at higher stimulation frequencies. In the presence of SK&F 83566 (10 micrograms/kg/min i.v.), a selective DA-1 receptor antagonist, fenoldopam no longer elicited significant inhibition of the preganglionic response. When postganglionic cardiac nerves were stimulated (0.5 Hz), fenoldopam (100 micrograms/kg/min i.v.) inhibited the response 55% with no significant effect at lower doses. Stimulation of sympathetic preganglionic fibers in the autoperfused hindlimb of the dog induced vasoconstriction. Fenoldopam (3 micrograms/kg/min i.a.) produced marked inhibition of nerve-induced constriction that was partially antagonized by SK&F 83566 (3 micrograms/kg/min i.a.). Complete inhibition of the effect of fenoldopam on sympathetic nerve stimulation in the hindlimb could not be achieved, as a component of this action was apparently due to postjunctional alpha-2 adrenoceptor blockade. This was evidenced by a reduction in the pressor response to the selective alpha-2 adrenoceptor agonist B-HT 920 by fenoldopam. These data indicate that fenoldopam stimulates DA-1 receptors in sympathetic ganglia to inhibit neurotransmission and this effect can be reversed by a selective DA-1 receptor antagonist.
Shebuski
R J
RJ
Fujita
T
T
Smith
J M
JM
Kopaciewicz
L J
LJ
Blumberg
A L
AL
Hieble
J P
JP
D000758:Anesthesia; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D018818:Fenoldopam; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000502:physiology; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D010477:Perfusion; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D013237:Stereoisomerism; D009435:Synaptic Transmission / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D001381:Azepines; D001552:Benzazepines; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D014665:Vasodilator Agents; D015016:Yohimbine; C024763:talipexole; D018818:Fenoldopam