Interaction of alpha-methyldopa with autonomic reflex tachycardia in man

Effects of alpha-methyldopa on cardiovascular reflexes were studied in normal healthy volunteers, and comparisons made with clonidine. Graded bicycle ergometer exercise and cumulative nitroprusside infusions were used as stimuli to autonomic reflexes. alpha-Methyldopa produced reduction in resting heart rate and a parallel shift in the stimulus-heart rate response relationship to nitroprusside and exercise 5 h after bolus intravenous dosing with 1,500 mg, but no effects at 0.5, 1.75, and 3 h during cumulative intravenous dosing with 1,875 mg. Clonidine produced a similar pattern of change in nitroprusside responses as early as 0.5 h after an intravenous dose of 300 micrograms. After atropine, alpha-methyldopa still produced a parallel shift in the nitroprusside stimulus-heart rate response relationship; however, clonidine reduced resting heart rate and abolished all increments in heart rate to nitroprusside infusion. Quantitative and qualitative differences in the effects of alpha-methyldopa and clonidine on autonomic reflexes in humans indicate differences in sites or mechanisms of action within the autonomic nervous system.