Importance of central serotonin neurons in the hypotensive action of methyldopa in the rat.
Normotensive (WKY) and stroke prone spontaneously hypertensive (SHR-SP) rats were given methyldopa (200 mg/kg i.p.) daily for five days and their brains were then sectioned and processed with the Faglu method for catecholamine fluorescence. This treatment with methyldopa induced a green fluorescence not seen in control animals, in cells coinciding with the B1-B9 groups of serotonin neurons in the brainstem. Pretreatment with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, i.c.v.), which is relatively specific for serotonin neurons, prevented the appearance of this green fluorescence in the serotonin cell groups of rats given methyldopa. Pretreatment with 5,7-DHT, i.c.v. approximately halved the magnitude of the hypotensive response to a single dose of methyldopa (80 mg/kg i.p.). We suggest that central serotonin nerves contribute to the hypotensive action of methyldopa. It is our hypothesis that methyldopa is taken up by these serotonin cells and that the green fluorescence reflects the production of alpha-methyldopamine, as a result of decarboxylation by the ubiquitous enzyme, L-aromatic amino acid decarboxylase.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D006651:Histocytochemistry; D006973:Hypertension / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D008636:Mesencephalon / Q000378:metabolism; D008750:Methyldopa / Q000378:metabolism / Q000494:pharmacology*; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*
D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D008750:Methyldopa; D009638:Norepinephrine