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

Am J Med. 1990 Oct;89(4):420-6. doi: 10.1016/0002-9343(90)90369-o.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Blood Pressure / physiology*
  • Cells, Cultured
  • Digitalis Glycosides / blood*
  • Dogs
  • Female
  • Humans
  • Hypertension / blood*
  • Hypertension / diet therapy
  • Hypertension / urine
  • In Vitro Techniques
  • Kidney Tubules / cytology
  • Kidney Tubules / metabolism
  • Male
  • Middle Aged
  • Ouabain / metabolism
  • Sodium / blood*
  • Sodium / pharmacokinetics
  • Sodium / urine
  • Sodium, Dietary / pharmacology
  • Tritium

Substances

  • Digitalis Glycosides
  • Sodium, Dietary
  • Tritium
  • Ouabain
  • Sodium