Mechanism of Action of Minoxidil Sulfate-Induced Vasodilation: A Role for Increased Potassium Permeability

The 1988 study investigated the mechanism of smooth muscle relaxing effect of minoxidil sulfate (MxSO4) in isolated rabbit superior mesenteric artery. The researchers found that MxSO4 effectively relaxed maximal norepinephrine contraction, but failed to relax 80 mM K+-induced contraction. The relaxation response to MxSO4 was significantly attenuated when the tissues were exposed to increased extracellular K+. The data suggested a role of K+ permeability during MxSO4 relaxation, which was further confirmed when it was found that MxSO4 can cause a significant stimulation of 42K efflux from the mesenteric artery preloaded with 42K. It was suggested that MxSO4 may act as a K+ channel agonist to affect the plasmalemmal Ca++ permeability during agonist activation. MxSO4 was demonstrated to cause an inhibition of NE-stimulated 45Ca influx in this tissue. The strong dependence on K+ permeability makes MxSO4 a unique vasodilator among the clinically used vasodilators.