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 microg 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 D1/2-like receptor agonist apomorphine (1-310 microg min-1), but not by the D2-like receptor agonist, bromocriptine (31-310 microg min.-1). In contrast, fenoldopam (1-310 microg 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 (alpha1/2; 2000 microg kg-1) or rauwolscine (alpha2; 100 microg kg-1), but remained unaffected after prazosin (alpha1; 100 microg kg-1) or haloperidol (D2-like; 1000 microg 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 microg 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 microg kg-1) or vagosympathectomy, were abolished by the D1-like receptor antagonist, SCH-23390 (10 microg 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 alpha2-adrenoceptors; and (ii) overshadow a vasodilator component, which involves vascular D1-like receptors.
Villalón
Carlos M
CM
Department of Pharmacobiology, CINVESTAV-IPN, Czda. de los Tenorios 235, Col. Granjas-Coapa, 14330 México D.F., México. carlos_villalon@infosel.net.mx
Ramírez-San Juan
Eduardo
E
Sánchez-López
Araceli
A
Bravo
Guadalupe
G
Willems
Edwin W
EW
Saxena
Pramod R
PR
Centurión
David
D
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology; D002342:Carotid Artery, External / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology* / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018818:Fenoldopam / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D014439:Tyramine / Q000494:pharmacology; D014628:Vagotomy; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D001971:Bromocriptine; D018818:Fenoldopam; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine; D014439:Tyramine