Evidence that the hypotensive action of methyldopa is mediated by central actions of methylnoradrenaline

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Abstract
Mean arterial blood pressure was recorded in conscious normotensive rats through indwelling arterial catheters. The effect of l-α-methyldopa (α-MD) (400 mg/kg, i.p.) was studied in animals pretreated with α-methyl-m-tyrosine (400 mg/kg i.p.) 27 and 15 h before α-MD, α-methyl-p-tyrosine methylester (H 44/68) (250 mg/kg, i.p.) 1 h before α-MD, and dl-α-hydrazino-α-methyl-β-(3,4-dihydroxyphenyl) propionic acid (MK 485, 100 mg/kg, i.p.) 30 min before α-MD. This pretreatment, which resulted in a severe depletion of endogenous catecholamines, did not alter the hypotensive effect of α-MD. The effect of α-MD (200 mg/kg, i.p.) was studied 30 min after pretreatment with the dopamine β-hydroxylase inhibitor, bis (4-methyl-l-homopiperazinyl-thiocarbonyl) disulphide (FLA-63) (25 mg/kg, i.p.). The hypotensive response to α-MD was completely abolished in these experiments. The formation of α-methylnoradrenaline from α-MD was prevented after FLA-63 but there was a significant increase in the amounts of α-methyldopamine formed.