Centrally Induced Hypotension by α-Methyldopa and α-Methylnoradrenaline in Normotensive and Renal Hypertensive Rats

Importance of Central Serotonin Neurons in the Hypotensive Action of Methyldopa in the Rat

“…The present experiment in WKY rats and SHR-SP confirm the fact that intraperitoneal injec- tions, in a dose range between 50 and 600 mg/kg, cause a dose dependent fall in blood pressure lasting up to 10 h (Nijkamp & de Jong, 1977).…”

“…Methyldopa is widely held to lower blood pressure through actions mediated predominantly by its effect on central catecholamine neurons (Finch & Haeusler, 1973;Day & Roach, 1974;Henning, 1975;Nijkamp & de Jong, 1977). Since many of the studies on the mode of action of methyldopa were carried out before it was appreciated that adrenaline was a central neurotransmitter (Hokfelt et al, 1974) and since we had recently demonstrated that the central noradrenaline (NA) and adrenaline (A) neurons in the medulla were topographically distinct (Howe et al, 1980), we were interested to see if methyldopa was taken up by the C1, C2 and C3 groups of adrenaline neurons (Hokfelt et al, 1974).…”

Effect of α-Methyldopa on α-Noradrenergic Receptor Binding Sites in the Mouse Brain

“…Renin is secreted into the blood from the kidney: in travenous infusion of a-MD produced a sig nificant fall in both mean arterial pressure and plasma renin activity in the dog; this suppression was abolished by pretreatment with carbidopa (an inhibitor of dopa decar boxylase) [6]. After simultaneous inhibition of peripheral as well as central dopamine-phydroxylase activity with FLA-63, no de crease in blood pressure and heart rate was observed after intraperitoneal administration of a-MD in renal hypertensive rats [16], Al though it has been generally understood that decarboxylation of a-MD in the central ner vous system is a prerequisite for its hypoten sive or behavioral depressant [5] action, it has not been clearly established whether amethyldopamine (a metabolite of decarboxy lation) [30], or a-methylnoradrenaline (a me tabolite of the subsequent P-hydroxylation) [8,9,16] or both [5] are the metabolites responsible for the above actions of a-MD.…”

“…Alpha-methyldopa (a-MD) has been shown to be a centrally acting [1,6,9] antihy pertensive agent [4,7,17], The site of this action was shown to be the level of the nucleus tractus solitarii in the medulla oblon gata [16,32]. Furthermore, the action is me diated by a-noradrenergic receptors [16].…”

Antihypertensive metabolites of alpha-methyldopa.

“…Rat forebrain was the tissue chosen for study because the sought adrenergic subtypes had been shown to be present here by previous investigators. 24 The methodology and results of our investigations have been presented elsewhere in detail. 25 Ranking in order of potency in competing with prazosin was ( -) E > ( -) N E > ( -)erythro-MNE > (-)erythro-ME > a-methyldopamine.…”