Vascular Dopamine Receptors in the Canine Hindlimb

Abstract

Increases in femoral blood flow were produced by intra-arterial injections of dopamine (5-50 Sg) in some but not all anaesthetized dogs studied, following treatment with the ca-adrenoceptor antagonist, phentolamine. 2 The dilator effect of dopamine was not due to inhibition of adrenergic vasomotor tone as it was not affected by pharmacological procedures which completely abolished the activity of vasomotor nerves.3 Blockade of vascular j-adrenoceptors using propranolol reduced the flow increases produced by dopamine much less than it did those produced by isoprenaline. 4 Responses to dopamine were significantly depressed by intra-arterial administration of ergometrine (0.5 mg). This dose of ergometrine did not reduce femoral dilator responses to acetylcholine, histamine, isoprenaline, bradykinin or 5-hydroxytryptamine. 5 It is concluded that the femoral vascular bed in the dog contains specific vasodilator receptors for dopamine. Ergometrine appears to be a selective antagonist of dopamine at these receptors.

Dopamine‐induced Neurogenic Vasodilatation in the Intact Hindleg of the Dog

“…Haloperidol, which selectively inhibits dopamine-induced ganglionic inhibition (Willems, 1973) and dopamine-induced neurogenic vasodilatation in the isolated perfused hindleg (Willems & Bogaert, 1975a), blocked the dopamineinduced decrease in femoral resistance without any influence on the reflex dilatation produced by (-)-noradrenaline. The direct vasodilator effect of dopamine in the femoral vascular bed, which is observed after aadrenoceptor blockade, has been attributed to f8-adrenoceptor stimulation (McNay & Goldberg, 1966) but others have found this effect to be resistant to _3-receptor blockade (Higgins et al, 1973), and antagonized by ergometrine (Bell et al, 1975). In our experiments, no a-receptor antagonist was given and intra-femoral dopamine elicited only a vasoconstriction.…”

“…Vasoconstriction also occurs when dopamine is injected directly into the innervated femoral artery (McDonald & Goldberg, 1963;McNay et a!., 1965). It is only after the administration of a-receptor antagonist drugs that the direct effect of dopamine on the femoral artery is a vasodilatation (McNay & Goldberg, 1966;Higgins, Millard, Braunwald & Vatner, 1973;Bell, Conway, Lang & Padanyi, 1975).…”

Localization of Vasodilator Dopamine Receptors in the Canine Hindlimb

“…This explains why McNay & Goldberg (1966) were unable to demonstrate the existence of dopamine-receptors using hind limbs with the paw circulation occluded. It also indicates that the difficulty encountered in producing femoral vasodilatation with dopamine unless a-adrenoceptor blockade has been produced (Eble, 1964;Bell et al, 1975) is due to concomitant dilatation and constriction in different parts of the limb. Nevertheless, even in the paw some a-adrenoceptor activation by dopamine was apparent, although stimulation of the putatively dopaminergic nerve supply to the paw produces only dilatation (Lang et al, 1976).…”

“…It is well documented that the canine vascular system contains specific dopamine receptors, activation of which produces vasodilatation (Eble, 1964;Goldberg, 1972;Higgins, Millard, Braunwald & Vatner, 1973;Bell, Conway & Lang, 1974;Bell, Conway, Lang & Padanyi, 1975). As well, dopamine activates vascular a-adrenoceptors, with resultant vasoconstriction (Hamet, 1931; Allwood, Cobbold & Ginsburg, 1963;Eble, 1964;McNay & Goldberg, 1966).…”

“…On the other hand, in the femoral vasculature, dopamine receptor-mediated vasodilatation is usually masked by simultaneous a-adrenoceptor activation. (Eble, 1964;Bell et al, 1975).…”