Clinical and biochemical approach of a circulating Na+-pump inhibitor

Inhibition of the activity of semipurified renal Na+, K+-ATPase and of 3H-Ouabain binding to erythrocytes was used to titrate the level of a plasmatic endogenous inhibitor of the Na+, K+-pump. The inhibition effect of plasma extracts was specific and unrelated to vanadate, calcium and products of proteolysis. Similar results were obtained with the two procedures. An endogenous pump inhibitor could be detected in 28 plasmas of the 42 normotensives investigated so far. In 18 out of 21 normotensives born of hypertensive parent(s) the level was found to be higher than that observed in normotensive controls devoid of hypertensive heredity. 13 untreated essential hypertensives out of 21 also exhibited higher levels of the sodium-potassium pump inhibitor. Plasma levels of the inhibitor appear stable during several months in male subjects. No clear relationship could be established either in normotensives or hypertensives between the pump inhibitor level, the urinary output of Na+, and blood pressure. Neither could any relationship be established between the inhibitor and the intraerythrocytic Na+ concentration. The accuracy of the methodology allows a large scale clinical investigation. It can also be used in the purification of the substance, and preliminary results precised that its molecular weight was inferior to 1 000 daltons and that it was anionic. Purified fractions were obtained after gel filtration, ion exchange chromatography, and high pressure liquid chromatography. Preliminary results suggest that the purified fraction may interfere with the mechanisms of hypertension. They inhibited the Na+-dependent serotonin uptake by human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)