Effects of DA-1- and DA-2-dopamine antagonists on apomorphine-induced inhibition of peripheral sympathetic neurotransmission.

1. Apomorphine, a dopamine receptor agonist, caused a dose-dependent inhibition of the electrically induced increase in diastolic blood pressure in the pithed rat. The anti-apomorphine effects of a range of dopamine antagonists with different DA-1/DA-2 selectivities were evaluated to characterize the dopamine receptor subtype(s) involved in this response. 2. Selective DA-2 antagonists domperidone and (-)-sulpiride and combined DA-2/DA-1 antagonists haloperidol, fluphenazine and (+)-sulpiride were active in this model, whereas the DA-1 antagonist SCH 23390 and the alpha-2 adrenoceptor antagonist idazoxan (RX-781094) were inactive. The rank order of potency of the dopamine antagonists was domperidone greater than fluphenazine greater than or equal to (-)-sulpiride greater than or equal to haloperidol greater than (+)-sulpiride much greater than SCH 23390. (-)-Sulpiride was about 25 times more potent than the (+)-isomer. 3. The observed antagonist profile suggests that the apomorphine-induced inhibition of neurogenic vasoconstriction in the pithed rat is mediated via dopamine receptors of the DA-2 subtype. The sympatho-inhibitory dopamine receptors in the cat heart have similar pharmacological characteristics. 4. The dopamine antagonists were devoid of influences on the vasoconstrictor response to electrical stimulation in the absence of apomorphine, whereas idazoxan potentiated it. This provides evidence against the participation of dopamine receptors in the modulation of the vasoconstrictor response to sympathetic stimulation in the pithed rat model.