Minoxidil: An Underused Vasodilator for Resistant or Severe Hypertension

Domenic A. Sica, MD

In This Article

Mechanism of Action

The antihypertensive activity of minoxidil is due to its sulphate metabolite, minoxidil sulfate. In large measure, minoxidil acts by opening adenosine triphosphate-sensitive potassium channels in vascular smooth muscle cells. The ensuing vasodilation is comparable to that observed with other known potassium channel openers, like pinacidil.[3] The predominant site of minoxidil action is arterial. Venodilation does not occur with minoxidil; thus, postural hypotension is unusual with its administration. The arteriolar vasodilation brought about by minoxidil can stimulate the peripheral sympathetic nervous system (SNS) by way of carotid and aortic baroreceptor reflexes. In conjunction with activation of the SNS, both pulse rate and cardiac output increase with minoxidil; however, cardiac output and heart rate will tend to revert to pretreatment values with long-term treatment.[4] Minoxidil administration also brings about an increase in plasma renin activity, largely due to the aforementioned activation of the SNS.[5,6,7] This activation of the renin-angiotensin axis further prompts increased biosynthesis of aldosterone; whereas plasma and urinary aldosterone levels are increased early in the course of treatment with minoxidil,[5,6,7] over time these values tend to normalize presumably because of accelerated metabolic clearance of aldosterone in association with hepatic vasodilation. [8] Although minoxidil is effective in reducing blood pressure (BP), the counterregulatory hemodynamic and neurohumoral changes that accompany its use can completely offset (or partially attenuate) the beneficial BP-lowering effect that ensues from arteriolar vasodilatation.[5]