Methyldopa and neural control of circulation in essential hypertension

The effects of methyldopa on hemodynamics at rest and on neural control of circulation were studied in subjects with essential hypertension. Blood pressure (recorded intraarterially), heart rate, cardiac output (thermodilution) and total peripheral resistance were measured before and after 15 to 20 days of continuous administration of the drug (500 to 750 mg twice daily). Methyldopa reduced mean arterial pressure (17 percent) and peripheral resistance (25 percent) without signlficantly affecting heart rate and cardiac output. The various cardiovascular responses to stimuli such as dynamic and isometric exercise and exposure to cold were un-changed by treatment with methyldopa, but the peak blood pressure values during these stimuli were lowered by methyldopa because of reduction of baseline values. Stimulation of carotid sinus baroreflexes (by negative air pressure in a sealed chamber enclosing the neck) also caused the same decrease in arterial pressure, peripheral resistance, heart rate and cardiac output before and during methyldopa treatment; on the other hand, the increase in arterial pressure and peripheral resistance caused by inactivation of baroreflexes (positive air pressure in the neck chamber) was somewhat reduced, although not abolished, by therapy with methyldopa. It is concluded that (1) the hypotensive effect of methyldopa is due to systemic vasodilatation; (2) this drug does not interfere with the cardiovascular responses to various neural excitatory stimuli; and (3) it reduces the ability of the carotid baroreflex to compensate for a decrease in blood pressure. Reduction of this pressor response may explain why methyldopa has a greater antihypertensive effect when patients are standing.