Central hypotensive action of alpha-methyldopa: an iontophoretic study in the cat

The central site and mechanism of alpha-methyldopa-induced hypotension were examined with the microiontophoretic technique which permits the topical application of drugs to single neurons of the bulbar vasomotor center in decerebrate cats. Cardiovascular neurons were identified by their response to an increase in arterial blood pressure following a small intravenous pressor dose of norepinephrine. Microiontophoretic application of alpha-methyldopa was found to have an inhibitory effect on the spontaneous firing rate of cardiovascular neurons. Furthermore, alpha-methyldopa was found to completely block the excitatory response of cardiovascular neurons to iontophoretically applied norepinephrine. Non-cardiovascular neurons, recorded from the same brain area, were unaffected by iontophoretic application of alpha-methyldopa at the same or greater doses that produced responses in cardiovascular neurons. While peripheral factors cannot be entirely ruled out, the present findings are contrary to the postulate that alpha-methyldopa lowers arterial blood pressure by stimulating central alpha-adrenoceptors, causing a reduction of sympathetic outflow to the periphery. Rather, the data indicate that alpha-methyldopa or its metabolites act directly on central alpha-adrenoceptors in a manner which results in reduced activity.