Marinobufagenin, an endogenous ligand of alpha-1 sodium pump, is a marker of congestive heart failure severity

Alexander I. Fridman, Sergei A. Matveev, Natalia I. Agalakova, Olga V. Fedorova, Edward G. Lakatta, Alexei Y. Bagrov

Research output: Contribution to journalArticle

Abstract

Background. A reduced cardiac output in chronic heart failure (CHF) evokes renal NaCl and water retention, and, therefore, activates mechanisms promoting natriuresis. Atrial natriuretic peptide (ANP) is one such factor. We hypothesized that another NaCl sensitive endogenous natriuretic factor, i.e., marinobufagenin (MBG), a specific ligand of the α-1 subunit of Na/K ATPase (the main kidney isoform) and also a vasoconstrictor and cardiotonic substance, would be elevated in CHF patients in a graded manner with the severity of CHF. Methods and results. We measured the plasma levels of MBG, α-hANP, ouabain-like compound (OLC) and left ventricular (LV) volumes and ejection fraction in 23 consecutive hypertensive male patients with CHF. Plasma MBG levels exhibited progressive increases (0.59 ± 0.15, 1.08 ± 0.20, 1.35 ± 0.17 and 1.88 ± 0.05 nmol/l NYHA 1-4, respectively) and paralleled the changes of α-hANP. Conversely, plasma OLC did not exhibit such increases. Plasma MBG correlated with α-hANP (r = 0.82; P < 0.0001). Both MBG and α-hANP correlated with LV systolic (r = 0.55 and r = 0.47; P < 0.01) diameter and inversely with ejection fraction (r = -0.73 and r = -0.60; P < 0.01). OLC did not exhibit correlations with α-hANP or LV volumes, but positively correlated with systolic brachial blood pressure and with pulse pressure. Conclusions. In CHF, MBG exhibits progressive increases similar to ANP, varies with CHF severity and correlates with LV systolic function. We hypothesize, that, in CHF, the concurrent production of these two natriuretic hormones, a vasorelaxant, ANP, and a vasoconstrictor, MBG, potentiate each other's natriuretic effects, but may offset their vasoactive actions.

Original languageEnglish (US)
Pages (from-to)1189-1194
Number of pages6
JournalJournal of hypertension
Volume20
Issue number6
DOIs
StatePublished - Jun 2002

Keywords

  • Bufanolides
  • Heart failure
  • Na(+)-K(+)-exchanging ATPase
  • Natriuretic peptides
  • Ouabain
  • Steroids

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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