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From the Laboratory of Pharmacology, Sechenov Institute of Evolutionary
Physiology and Biochemistry (A.Y.B., R.I.D., E.A.K.), and Verta Peptides Inc
(V.M.S.), St Petersburg, Russia; Laboratory of Cardiovascular Science,
National Institute on Aging, Baltimore, Md (A.Y.B., O.V.F.); and Department of
Medicinal Chemistry, Mass Spectrometry Center, University of Washington,
Seattle (W.N.H., A.P.H.).
Abstract—Recent evidence suggests
the existence of several endogenous
Na+,K+-ATPase inhibitors in
mammals. Previously, we have shown that the amphibian
Na+,K+-ATPase inhibitor
marinobufagenin (3,5-dihydroxy-14,15-epoxy bufodienolide) acts as a
vasoconstrictor in isolated rat and human arteries. Mammalian plasma
was shown to contain marinobufagenin-like immunoreactive material,
which is responsive to saline volume expansion. The present study
describes purification of a bufodienolide, which is similar to
marinobufagenin, from the urine of patients after acute myocardial
infarction with the use of thin-layer chromatography
and reverse-phase high-performance liquid
chromatography (HPLC). The purified substance
cross-reacted with marinobufagenin antibody, demonstrated maximal UV
absorbance at 300 nm characteristic of bufodienolides, and eluted from
HPLC columns with the same retention time as marinobufagenin. Mass
spectrometry of purified material revealed the presence of a substance
indistinguishable from amphibian marinobufagenin and having molecular
mass of 400 D. The present studies show that one of the human
digitalis-like factors may have a bufodienolide structure and is likely
to represent marinobufagenin or its isomer, and they suggest a
role for this substance in the pathogenesis of myocardial
ischemia.
© 1998 American Heart Association, Inc.
Scientific Contributions
Characterization of a Urinary Bufodienolide Na+,K+-ATPase Inhibitor in Patients After Acute Myocardial Infarction
Key Words: Na+-K+-ATPase • bufodienolides • myocardial infarction • digitalis-like factors
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