Effects of dopaminergic drugs on the sympathoadrenal system.
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 40 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Faculté de Médecine, Laboratoire de Pharmacologie Médicale et Clinique, France.
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Damase-Michel
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Montastruc
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Tran
D000311:Adrenal Glands / Q000187:drug effects*; D000758:Anesthesia; D000818:Animals; D002946:Cisterna Magna / Q000502:physiology; D004285:Dogs; D015259:Dopamine Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D018818:Fenoldopam / Q000008:administration & dosage / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007267:Injections; D007275:Injections, Intravenous; D008297:Male; D009121:Muscle Denervation; D017447:Receptors, Dopamine D1 / Q000819:agonists; D012849:Sinoatrial Node; D013564:Sympathetic Nervous System / Q000187:drug effects*
D015259:Dopamine Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D018818:Fenoldopam; D006220:Haloperidol