Potassium, Na+-K+ pump inhibitor and low-renin hypertension.

A local increase in extracellular potassium concentration [K+]o, up to about 8 mEq/liter, by topical application or intra-arterial infusion of iso-osmotic solutions of K+ salts, causes arteriolar dilation and decreased resistance to blood flow in systemic vascular beds. A local decrease in [K+]o over physiologic ranges induces arteriolar constriction and increased resistance to blood flow. K+ vasodilation is accompanied by hyperpolarization of the smooth muscle cell, whereas the vasoconstriction is accompanied by depolarization. All of these responses can be blocked by ouabain, a potent Na+,K+-ATPase inhibitor. Thus it is thought that K+ vasodilation results from stimulation of the electrogenic Na+-K+ pump, and that the constriction results from its inhibition. Acute generalized inhibition of the Na+,K+-ATPase and Na+-K+ pump (hypokalemia, strophanthidin, methylguanidine, vanadate) in the anesthetized dog can raise blood pressure. In experiments in animals, myocardial Na+,K+-ATPase and vascular Na+-K+ pump activities were decreased in low-renin hypertension, and vascular Na+-K+ pump activity was decreased following acute volume expansion, changes associated with bioassay evidence of a Na+-K+ pump inhibitor in the plasma. The inhibitor appears to arise in, or to be influenced by the area of the anteroventral third ventricle of the brain. It induces electrogenic depolarization of vascular smooth muscle cells and may inhibit norepinephrine uptake by adrenergic nerve terminals. Potassium and a circulating endogenous Na+,K+-ATPase inhibitor of unknown molecular structure may partly regulate the mechanical activity of cardiovascular muscle and participate in the genesis of certain forms of hypertension. Potassium may be of value in the prevention and therapy of hypertension, partly by virtue of its vasodilator activity.