Further evidence for a central hypotensive action of α-methyldopa in both the rat and cat

TLDR: The results strongly suggest that the central actions of α‐methyldopa are important for its hypotensive effect, although a possible peripheral effect cannot be excluded.

Abstract: 1. α-Methyldopa (300 mg/kg i.p.) produced a fall in blood pressure in conscious genetic hypertensive rats. Pretreatment with intraventricular 6-hydroxydopamine prevented this hypotensive effect of α-methyldopa, whilst intravenous 6-hydroxydopamine reduced but did not prevent the hypotension. 2. The hypotensive effect of α-methyldopa was prevented or reversed by intraventricular injection of phentolamine (200 μg/rat). 3. Pressor responses obtained by stimulation of the entire sympathetic outflow in the Gillespie & Muir preparation, were unaffected by pretreatment with α-methyldopa (300 mg/kg i.p.). 4. Vasoconstrictor responses to periarterial nerve stimulation of the isolated renal artery preparation of the rat were markedly reduced by pretreatment with α-methyldopa. Furthermore, α-methylnoradrenaline was found to have one-eighth the vasoconstrictor potency of noradrenaline in this particular artery preparation. 5. Pressor responses obtained by stimulation of the posterior hypothalamus or midbrain reticular formation in the rat anaesthetized with urethane were markedly reduced by pretreatment with α-methyldopa. FLA-63, a selective dopamine-β-hydroxylase inhibitor, prevented the reduction of the pressor responses to hypothalamic stimulation produced by α-methyldopa. 6. Stimulation of the posterior hypothalamus in the anaesthetized cat caused both an increase in sympathetic nerve activity and a rise in blood pressure. These responses were markedly reduced 3-4 h after the injection of α-methyldopa (100 mg/kg i.v.). 7. These results strongly suggest that the central actions of α-methyldopa are important for its hypotensive effect, although a possible peripheral effect cannot be excluded.