Pharmacological profile of the vascular responses to dopamine in the canine external carotid circulation

The present study investigated the effects of dopamine on the canine external carotid circulation. One min. intracarotid artery (i.c.) infusions of dopamine (10-310 μg min.^-1) produced dose-dependent decreases in the canine external carotid conductance without affecting blood pressure or heart rate. This effect was mimicked by the D_1/2-like receptor agonist apomorphine (1-310 μg min^-1), but not by the D₂-like receptor agonist, bromocriptine (31-310 μg min.^-1). In contrast, fenoldopam (1-310 μg min.^-1, intracarotid), a D₁-like receptor agonist, produced dose-dependent increases in external carotid conductance. The vasoconstrictor response to dopamine was abolished after intravenous administration of the antagonists, phentolamine (α_1/2; 2000 μg kg^-1) or rauwolscine (α₂; 100 μg kg^-1), but remained unaffected after prazosin (α₁; 100 μg kg^-1) or haloperidol (D₂-like; 1000 μg kg^-1). Interestingly, after phentolamine not only were the vasoconstrictor responses to dopamine abolished, but even a dose-dependent vasodilator component was unmasked. These vasodilator responses to dopamine remained unchanged after intravenous haloperidol or propranolol (1000 μg kg^-1 each). On the other hand, the vasodilator responses to fenoldopam, which remained unchanged after intravenous saline (0.1 ml kg^-1), propranolol (1000 μg kg^-1) or vagosympathectomy, were abolished by the D₁-like receptor antagonist, SCH-23390 (10 μg kg^-1). Lastly, the responses to dopamine and fenoldopam were not significantly altered after intraperitoneal pretreatment with reserpine (5 mg kg^-1; -24 hr). The above results suggest that the canine external carotid vasoconstrictor responses to dopamine: (i) are mainly mediated by α₂-adrenoceptors; and (ii) overshadow a vasodilator component, which involves vascular D₁-like receptors.