Digitalis-like activity in human plasma: Relation to blood pressure and sodium balance

Abstract

purpose: On the assumption that renal tubular cells are more important as the target cells for a natriuretic factor than blood cells, we used a well-characterized cultured renal tubular cell line, Madin-Darby canine kidney (MDCK) cells, to monitor the circulating digitalis-like factor in human plasma and examine its role in the regulation of blood pressure and sodium balance. subjects and methods: We investigated the effects of plasma on binding of radioactive ouabain to monolayered MDCK cells in order to determine the level of a circulating digitalis-like factor. First, we measured specific 3H-ouabain binding to MDCK cells in the presence of plasma from 71 outpatients (34 normotensive subjects and 37 hypertensive patients) after incubation for 4 hours. Second, we measured specific 3H-ouabain binding after incubation of cells with plasma from 16 hospitalized subjects (eight normotensive subjects and eight hypertensive patients) receiving low and high sodium diets. results: In Study 1, ouabain binding was lower by 30% with plasma from hypertensive patients than with plasma from normotensive subjects (p <0.01). There was a significant negative correlation between individual subject's systolic or mean blood pressure and ouabain binding (r = −0.34, p <0.01 or r = −0.29, p <0.01). In Study 2, ouabain binding was also significantly reduced by 25% in the presence of plasma from hypertensive subjects as compared with plasma from normotensive subjects irrespective of sodium intake (p <0.01). A significant negative correlation was also found for all subjects between either systolic, diastolic, or mean blood pressure and ouabain binding (r = −0.58, p <0.01, r = −0.51, p <0.01, or r = −0.55, p <0.01, respectively). With the changes from low to high sodium intake, there was a corresponding decrease in ouabain binding (p <0.01) and an increase in sodium excretion (p <0.01). A significant negative correlation was observed between these two parameters (r = −0.47, p <0.05). conclusions: These findings suggest that a circulating digitalis-like factor, which may act on renal tubular cells as the ouabain-displacing compound, is increased in patients with essential hypertension and also demonstrate that plasma levels may be influenced by changes in dietary sodium intake.