Effects of dopamine (DA) and SKF 82526, a selective DA1-receptor agonist, on vascular resistances in the canine forelimb

GJ Grega, RJ Barrett, SW Adamski and MF Lokhandwala

This study was performed to determine the presence of vascular dopamine (DA1) receptors in the canine forelimb. Local i.a. infusions of DA (2, 4 or 8 micrograms base/min) produced cutaneous and skeletal muscle vasoconstriction in the forelimb comparable to that produced by local i.a. infusions of norepinephrine (0.5, 1 or 4 micrograms base/min). In the cutaneous vasculature, DA produced large artery, small vessel and large vein constrictions. The small vessels and large veins constricted proportionately more than the large arteries. The pattern of constriction produced by DA along the cutaneous vascular tree was similar to that produced by norepinephrine. The forelimb vasoconstriction produced by both DA and norepinephrine was abolished completely by treatment with phentolamine, indicating that both agents produce vasoconstriction mediated by stimulation of alpha adrenoceptors. The failure of DA to produce vasodilation after phentolamine suggests that there are no vascular or DA1-subtype DA receptors in the canine forelimb vasculature. The local i.a. infusion of SKF 82526, a selective DA1-receptor agonist, for 3 min produced cutaneous and skeletal muscle dilation which could be antagonized by either sulpiride or phentolamine. This neurogenic dopaminergic vasodilation produced by SKF 82526 (25, 50 or 100 micrograms base/min) was converted into vasoconstriction after ganglionic blockade. Inasmuch as SKF 82526 does not activate presynaptic or DA2-subtype DA receptors, the neurogenic vasodilation caused by SKF 82526 may be due to a dopaminergic inhibition of ganglionic transmission. Whereas the results of our study fail to provide any evidence for the presence of vascular DA (DA1) receptors in the canine forelimb, they show that SKF 82526, a DA1-receptor agonist, produces neurogenic vasodilation probably by activating ganglionic DA receptors.

Volume 229, Issue 3, pp. 756-762, 06/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics