Evidence for a circulating endogenous Na+-K+ pump inhibitor in low-renin hypertension

It is now more than 10 years since we suggested that an endogenous Na+,K+-ATPase inhibitor might participate in the genesis of certain forms of ren hypertension. Although the question is not yet fully resolved, there has been much activity in the area. We here review that activity. In 1980 we reported that supernatant of boiled plasma from dogs with one-kidney, one wrapped hypertension reduces Na+-K+ pump activity when applied to an artery from another animal. Since then, we and a number of other investigators have described Na+-K+ pump inhibitory activity in the plasma of animals and humans with hypertension, particularly the low-renin varieties. The activity results from a heat-stable small molecule, but the chemical structure of the molecule is unknown. It appears to be released from the hypothalamus in response to pulmonary vascular distension and to act on blood vessels via electrogenic depolarization. Although it may be sufficient by itself to raise pressure, it may be most effective when superimposed on vascular smooth muscle cells that are abnormally permeable to Na+. Efforts to determine the chemical structure of the agent or agents should be intensified.