Effects of SK&F 85174, a DA-1/DA-2 receptor agonist, on pre- and postganglionic sympathetic neurotransmission to the heart.
We have performed experiments to determine the effects of SK&F 85174, a mixed DA-1/DA-2 receptor agonist, on the tachycardia elicited during pre- and postganglionic stellate stimulation in anesthetized dogs in order to identify a possible action of this compound on the stellate ganglia. SK&F 85174 produced hypotension and caused significant impairment of positive chronotropic responses elicited during pre- and postganglionic stellate stimulation. Pharmacological analysis of SK&F 85174-induced inhibition of cardiac sympathetic function with selective DA-1 and DA-2 receptor antagonists revealed that prior treatment with either S-sulpiride or domperidone (DA-2 receptor antagonists) significantly attenuated the inhibitory effects of SK&F 85174 on responses to pre- and postganglionic stellate stimulation. R-sulpiride (DA-1 receptor antagonist) failed to antagonize SK&F 85174-induced inhibition of tachycardia elicited during preganglionic stellate stimulation. Pretreatment with SCH 23390 (DA-1 receptor antagonist) did not modify the inhibitory effect of SK&F 85174 on responses to postganglionic nerve stimulation. However, SCH 23390 was most effective in antagonizing the hypotensive effect of SK&F 85174. These results show that SK&F 85174 inhibits sympathetic neurotransmission to the heart by activating presynaptic and possibly ganglionic DA-2 receptors, whereas the hypotension produced by SK&F 85174 results predominantly from the activation of the vascular DA-1 receptors. SK&F 85174 does not seem to exert any effect on the ganglionic DA receptors which are reported to be activated by the selective DA-1 receptor agonist, fenoldopam.
Dlewati
A
A
Department of Pharmacology, College of Pharmacy, University of Houston, TX 77204-5515.
Watkins
H O
HO
Lokhandwala
M F
MF
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D004285:Dogs; D004294:Domperidone / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D005260:Female; D005725:Ganglia, Autonomic / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D013233:Stellate Ganglion / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D001552:Benzazepines; D015259:Dopamine Agents; D011954:Receptors, Dopamine; D004294:Domperidone; C045977:SK&F 85174