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

Abstract

I The dopamine-induced neurogenic vasodilatation, previously described in the isolated perfused hindleg of the dog, has been studied in anaesthetized dogs with intact circulation in the hindleg. Dopamine was administered intravenously and/or intra-aortically, either as a bolus injection of 4 or 16 JLg/kg, or as a continuous infusion of 4, 8, 16 or 32 gg kg-' min-'. 2 Dopamine, given as a bolus injection or by infusion, reversibly inhibited synaptic transmission in the paravertebral lumbar ganglia, studied with preganglionic stimulation at 1 Hz. The inhibitory effect decreased gradually when the frequency of stimulation was increased to 16 Hz. The inhibition by dopamine was also present when spontaneous postganglionic activity was recorded. These effects were more pronounced on intra-aortic than on intravenous administration of dopamine. 3 In about half of the animals studied, injection or infusion of dopamine elicited a decrease of vascular resistance in the innervated femoral artery, whereas systemic blood pressure either did not change or decreased. In the denervated femoral artery, an increase in vascular resistance was always observed. 4 The decrease in femoral vascular resistance was considered to correspond with neurogenic vasodilatation caused by paravertebral ganglionic inhibition since (i) it only occurred in the innervated hindleg, (ii) blood pressure did not rise, (iii) this decrease was insensitive to atropine or propranolol and (iv) it was blocked by small doses of haloperidol. When hypovolemic shock was produced, the incidence of the neurogenic decrease of vascular resistance was smaller. S Dopamine also increased renal blood flow. This increase was not reduced by the occurrence of the neurogenic vasodilatation in the innervated femoral artery. 6 These results are consistent with the idea that the dopamine-induced neurogenic vasodilatation, originally described in the isolated perfused hindleg of the dog, also occurs when the circulation to the hindleg is intact. This suggests that, in the dog, the inhibitory effect of dopamine on sympathetic ganglia modulates its peripheral vasoconstrictor effects. In hypovolemic shock, where sympathetic nervous activity is high, the inhibitory effect of dopamine on sympathetic ganglia disappears and its direct vasoconstrictor effect on the vessels dominates.

Cardiovascular Dopamine Receptors: Physiological, Pharmacological and Therapeutic Implications

“…Our experiments with ganglionic blocking agents and reserpine directly support this notion (Lokhandwala & Jandhyala, 1979). Additional evidence for such an action has been reported by other investigators as well (Willems & Bogaert, 1973;Morishita & Furukawa, 1974;Bogaert et al, 1977). Following blockade of ganglionic transmission, dopamine exerts on a-adrenoreceptor-mediated vasoconstriction (Fig.…”

“…For example, activation of presynaptic dopamine receptors would cause an inhibition of noradrenaline release and consequently passive vasodilatation. Activation of ganglionic dopamine receptors would be predicted to inhibit ganglionic transmission, decrease sympathetic vasoconstrictor discharge and thus lead to passive vasodilatation (Willems & Bogaert, 1973;Buylaert & Willems, 1976;Bogaert et al, 1977;Buylaert, Willems & Bogaert, 1977;Laubie, Schmitt & Falq, 1977;Lokhandwala & Buckley, 1977b). Likewise, it is possible that a dopamine receptor antagonist would be able to inhibit the vasodilatation by antagonizing not only the musculotropic dopamine receptor as suggested previously, but also the neurotropic dopamine receptors.…”

Ganglionic Dopamine Receptors as Mediators of the Inhibition of Neurogenic Vasoconstriction Produced by Fenoldopam

“…Therefore, activation of putative dopamine receptors located at sympathetic ganglia may have been responsible for the inhibitory action of fenoldopam. The presence of a dopamine receptor in sympathetic ganglia has been previously reported (Willems & Bogaert, 1975;Bogaert, DeShaepdryver & Willems, 1977), and it is shown that dopamine causes neurogenic dilation by inhibiting synaptic transmission in the lumbar ganglia, an action antagonized by haloperidol (Bogaert et al, 1977).…”

Dopamine receptor agonists in cardiovascular therapy

“…These include the outer surface of the membrane of the postganglionic sympathetic nerve terminal (presynaptic), the sympathetic ganglia (ganglionic) and the cardiovascular control centers within the central nervous system [Lokhandwala, 1979a;Starke, 1981;Bogaert et al, 1977;Kushiku et al, 1980;Barrett and Lokhandwala, 1982a;Kondo et al, 1981a,b]. Although dopamine acts as an agonist at these receptors, it is not selective for DA2 receptors.…”

“…While the participation of these dopamine receptors in the overall actions of dopaminergic agonists remains to be determined, it is reported that activation of central nervous system dopamine receptors produces an inhibition of central sympathetic outflow and a subsequent lowering of blood pressure and heart rate [Kondo et al, 1981a,b;Barrett and Lokhandwala, 1982a;Cavero et al, 1982b]. Dopamine receptor agonists can also activate dopamine receptors located at the sympathetic ganglia and inhibit ganglionic transmission, which would also cause hypotension and bradycardia [Lin and Willems, 1974;Bogaert et al, 1977;Kitzen et al, 1979;Lokhandwala and Jandhyala, 19791. Finally, activation of presynaptic dopamine receptors located on postganglionic sympathetic nerve terminals results in the inhibition of norepinephrine release during sympathetic nerve stimulation [Enero and Langer, 1975;Fuder and Muscholl, 1978;Lokhandwala and Buckley, 1977a.b;Dubocovich and Langer, 19801.…”