Digitalis-like activity in human plasma: relation to blood pressure and sodium balance.
OBJECTIVE
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.


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 less than 0.01). There was a significant negative correlation between individual subject's systolic or mean blood pressure and ouabain binding (r = -0.34, p less than 0.01 or r = -0.29, p less than 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 less than 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 less than 0.01, r = -0.51, p less than 0.01, or r = -0.55, p less than 0.01, respectively). With the changes from low to high sodium intake, there was a corresponding decrease in ouabain binding (p less than 0.01) and an increase in sodium excretion (p less than 0.01). A significant negative correlation was observed between these two parameters (r = -0.47, p less than 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.
Goto
A
A
Second Department of Internal Medicine, University of Tokyo, Japan.
Yamada
K
K
Ishii
M
M
Sugimoto
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002478:Cells, Cultured; D004071:Digitalis Glycosides / Q000097:blood*; D004285:Dogs; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000178:diet therapy / Q000652:urine; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010042:Ouabain / Q000378:metabolism; D012964:Sodium / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine; D012982:Sodium, Dietary / Q000494:pharmacology; D014316:Tritium
D004071:Digitalis Glycosides; D012982:Sodium, Dietary; D014316:Tritium; D010042:Ouabain; D012964:Sodium