(Hypertension. 2001;37:462.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Marinobufagenin, an Endogenous 
-1 Sodium Pump Ligand, in Hypertensive Dahl Salt-Sensitive Rats
From the Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, Baltimore, Md (O.V.F., N.I.A., E.G.L., A.Y.B.), and Institute of Highly Pure Biopreparations, St. Petersburg, Russia (N.I.K.).
Correspondence to Alexei Y. Bagrov, Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224. E-mail bagrovA{at}grc.nia.nih.gov
Dahl
salt-sensitive rats (DS), which have a mutation in the 
-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 -1 than -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 -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 -1
Na+/K+-ATPase
ligand, MBG, is elaborated to promote natriuresis in hypertensive DS.
MBG acts as a selective inhibitor of the
ouabain-resistant -1
Na+/K+-ATPase
subunit, ie, the major sodium pump isoform of the kidneys, as would be
expected of a putative natriuretic hormone.
Key Words: NaCl • Dahl rats • Na+/K+-ATPase • kidney • bufadienolides • marinobufagenin
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