Centrally mediated increased reflex vagal bradycardia after L-dopa in monoamine oxidase-inhibited anesthetized dogs.
In monoamine oxidase-inhibited dogs whose peripheral dopa decarboxylase was inhibited with MK-486, L-dopa (K mg/kg i.v.) caused significant hypotension and bradycardia. In addition, reflex bradycardia but not pressor responses to norepinephrine were markedly enhanced by the drug. Similar results were obtained after intracerebroventricular administration of L-dopa (0.5 mg/kg) in monoamine oxidase-inhibited dogs not receiving MK-486. Proparnolol prevented the bradycardia caused by L-dopa but was without effect on the reflex facilitation. Both atropine and phentolamine had no effect on L-dopa bradycardia but prevented the facilitatory effect on reflexes. Inhibition of both peripheral and central dopa decarboxylase with Ro 4-4602 prevented all the effects of L-dopa. Infusions of dopamine which had obvious cardiovascular effects had no effect on reflex responses to norepinephrine. It is concluded that L-dopa, after decarboxylation, causes a centrally mediated enhancement of reflex vagal bradycardia. Pharmacological analysis of this enhancement suggests that this effect appears to be a result of central alpha receptor stimulation.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001545:Benserazide / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002230:Carbidopa / Q000494:pharmacology; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*
D008996:Monoamine Oxidase Inhibitors; D007980:Levodopa; D001545:Benserazide; D001285:Atropine; D011433:Propranolol; D002230:Carbidopa; D004298:Dopamine; D009638:Norepinephrine; D010646:Phentolamine