Role of ouabain-like factors and Na-K-ATPase inhibitors in hypertension--some old and recent findings.

Three lines of evidence led to our suggestion in 1976 that sodium pump inhibitors are involved in volume expanded hypertension. These were 1) pressor activity of low renin hypertensive blood 2) natriuretic and sodium pump inhibiting activities of volume expanded blood and 3) potassium vasoactivity which was blocked by ouabain and suppressed potassium vasodilatation, myocardial Na-K-ATPase, and artery, vein and WBC sodium pumps in low renin hypertension. This led to bioassay of plasma from acutely volume expanded dogs and from dogs with one-kidney, one wrapped hypertension for sodium pump inhibiting activity that acts on arteries. Positive results were reported in 1980. The assay was also positive in rats with one-kidney, one clip and reduced renal mass hypertension (but not in rats with spontaneous or salt sensitive hypertension) and in humans with acute volume expansion and low renin essential hypertension (but not in humans with normal renin hypertension). Thus the inhibitor which acts on the sodium pump in arteries appears to be present only in low renin hypertension.