Is a circulating sodium transport inhibitor involved in the pathogenesis of essential hypertension?

There is controversy about the relationship between sodium intake and the prevalence of high blood pressure. Part of this controversy relates to how an increase in sodium intake could cause an increase in peripheral resistance. We have put forward the following hypothesis. In essential hypertension there is an inherited defect of the kidney's ability to excrete sodium which becomes increasingly obvious the greater the sodium intake. This difficulty in sodium excretion by the kidney increases the concentration of a circulating sodium transport inhibitor that affects sodium transport across many cell membranes. In the kidney the inhibitor adjusts urinary sodium excretion back towards normal so that sodium balance is near that of normal subjects on the same intake of sodium. In the arteriolar smooth muscle the inhibition of sodium transport across the cell wall causes a rise in intracellular sodium concentration which, in turn, raises the intracellular calcium concentration and thus increases vascular reactivity. This hypothesis also proposes that the abnormalities of sodium transport in circulating cells in vivo are directly due to the increased secretion of the circulating sodium transport inhibitor. Evidence supporting this hypothesis is discussed. Firstly, it is pointed out that there is much evidence which suggests that there is a circulating inhibitor of Na+-K+-ATPase, the level of which is related to sodium intake and that the level of this inhibitor appears to be increased in many hypertensives. Secondly, the finding that normotensive white cells incubated in the plasma of hypertensive patients develop the same decrease in the Na+-K+-ATPase dependent sodium transport as the hypertensives own white cells also suggests that hypertensives have an increase in a circulating Na+-K+-ATPase inhibitor.