Evidence for a circulating sodium-potassium pump inhibitor in low renin hypertension

In 1978, we reported that supernate of boiled plasma from acutely volume expanded dogs and rats reduces sodium-potassium pump activity when applied to the tail artery from a normal rat and then in 1980 we reported that the same is the case for plasma supernate from the dog with one-kidney, one wrapped hypertension, a model of low renin hypertension. Since then, we and a number of other investigators have described sodium-potassium pump inhibitory activity in the plasma of animals and humans with hypertension, particularly of the low renin variety. The activity results from a heat stable small molecule, probably the putative natriuretic hormone. It appears to be released from the hypothalamus in response to cardiopulmonary vascular distention subsequent to failure of the kidney to excrete the prevailing sodium and water intake. It probably acts on blood vessels both directly (electrogenic depolarization) and indirectly (inhibition of norepinephrine reuptake into adrenergic nerve terminals). While it may be sufficient by itself to raise blood pressure, it may be most effective when superimposed on vascular smooth muscle cells which are abnormally permeable to sodium. Efforts to determine its chemical structure should be intensified.