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.