Marinobufagenin, an endogenous α-1 sodium pump ligand, in hypertensive Dahl salt-sensitive rats

Olga V. Fedorova, Nikolai I. Kolodkin, Natalia I. Agalakova, Edward G. Lakatta, Alexei Y. Bagrov

Research output: Contribution to journalArticlepeer-review

Abstract

Dahl salt-sensitive rats (DS), which have a mutation in the α-1 subunit of Na+/K+ATPase, exhibit impaired pressure natriuresis and on a high-salt diet, retain Na+ and exhibit increased blood pressure. Recently, we have shown that mammalian tissues contain a bufadienolide Na+/K+-ATPase inhibitory factor, marinobufagenin (MBG), that exhibits greater affinity for the α-1 than α-3 sodium pump isoform. The present study investigated the possible role of MBG in hypertension in DS on a high NaCl intake. Eight DS and 8 Dahl salt-resistant rats (DR) were placed on an 8% NaCl diet. Within 2 weeks, systolic blood pressure increased in DS (162±9 mm Hg at week 2 versus 110±2 mm Hg in baseline, P<0.01), and increased less in DR (124±3 mm Hg at week 2 versus 112±2 mm Hg in baseline). Renal excretion of MBG increased 4-fold (38.9±7.6 pmol versus 9.1±1.3 pmol in baseline, P<0.01) in DS, but by only 25% in DR (13.2±0.9 pmol versus 10.3±0.7 pmol in baseline). Excretion of endogenous ouabain did not change in either strain. MBG-immunoreactive material was purified from the urine of hypertensive DS by means of 2 steps of reverse-phase high performance liquid chromatography (HPLC) and compared with plant ouabain and amphibian MBG for its ability to inhibit the Na+/K+-ATPase from rat kidney (which expresses only α-1 Na+/K+-ATPase isoform). Unlike ouabain (IC50=248 μmol/L), serially diluted, HPLC-purified MBG immunoreactivity from DS and authentic MBG potently inhibited rat kidney Na+/K+-ATPase (IC50=70 and 78 nmol/L. respectively). Our results suggest that an α-1 Na+/K+-ATPase ligand. MBG, is elaborated to promote natriuresis in hypertensive DS. MBG acts as a selective inhibitor of the ouabain-resistant α-1 Na+/K+-ATPase subunit, ie. the major sodium pump isoform of the kidneys, as would be expected of a putative natriuretic hormone.

Original languageEnglish (US)
Pages (from-to)462-466
Number of pages5
JournalHypertension
Volume37
Issue number2 II
DOIs
StatePublished - 2001

Keywords

  • Bufadienolides
  • Dahl rats
  • Kidney
  • Marinobufagenin
  • Na/K-ATPase
  • NaCl

ASJC Scopus subject areas

  • Internal Medicine

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