Effects of Dopaminergic Drugs on the Sympathoadrenal System

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Several studies have suggested that dopamine (DA) plays a major role in cardiovascular functions. Dopaminergic receptors have been found on sympathetic nerve terminals (DA2), kidney (DA1, DA2), vascular smooth muscle (DA1) as well as on sympathetic ganglia (DA1, DA2) and adrenal gland (DA1, DA2). Previous studies have shown that DA2 receptor stimulation by a specific DA2 agonist, quinpirole (1) elicits a peripheral depressor action (decreased blood pressure) and a central pressor component involving an increase in both sympathetic tone and vasopressin release and (2) does not affect under in vivo conditions adrenal catecholamine release. The present study investigates the effects of fenoldopam, a specific DA1 receptor agonist on both cardiovascular responses and catecholamine release from the adrenal medulla. In conscious normal dogs, fenoldopam (10, 20 and 40μg/kg i.v.) elicited a decrease in blood pressure and a marked increase in heart rate associated with a rise in plasma catecholamine levels. The increase in heart rate is only due to baroreflex mechanism since fenoldopam (conversely to DA2 receptor agonists like quinpirole) does not exert a central excitatory component (as shown by the absence of cardiovascular effects after intracisternal injection). Moreover, in sinoaortic denervated dogs (i.e. animals deprived from baroreflex pathways), the decrease in arterial blood pressure was more important than in normal dogs. Heart rate was unchanged. In these animals, DA1 stimulation induced a decrease in sympathetic tone, as shown by the significant fall in plasma noradrenaline levels. These "in vivo" data clearly demonstrate the inhibitory role of ganglionic DA1 receptors. In anesthetized dogs, fenoldopam (5μg/kg/min i.v.) failed to modify catecholamine release from the adrenal medulla whatever the stimulation frequencies (1, 3 and 5Hz) of the sectioned splanchnic nerve. Thus, using DA agonists (DA1: fenoldopam or DA2: quinpirole see above), we failed to demonstrate any potential role of adrenal dopamine receptors in the control of catecholamine release under in vivo conditions. Since in vivo studies carried out in normal subjects with domperidone, a DA2 receptor antagonist, suggest a modulatory role for adrenal DA receptor during high sympathetic stimulation induced by physical exercise, we further investigate in anesthetized dogs the effects of DA antagonists on adrenal catecholamine release. After blockade of alpha and beta adrenergic receptors, we found that haloperidol (1mg/kg i.v.) elicited an increase in noradrenaline release from the adrenal medulla. In conclusion, the use of appropriate experimental models in dogs (sinoaortic denervation, chronic implanted intracisternal cannula and in vivo catheterism of adrenal vein) allows us to demonstrate (1) that the stimulation of ganglionic DA1 receptors induced a decrease in noradrenaline release due to the inhibition of ganglionic transmission and (2) that, under in vivo conditions, the blockade of DA receptors by haloperidol allows to reveal the inhibitory role of adrenal DA receptors on the release of adrenal catecholamines. (Hypertens Res 1995; 18 Suppl. I: S119-S124)

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