Document Detail

Marinobufagenin, an endogenous alpha-1 sodium pump ligand, in hypertensive Dahl salt-sensitive rats.
MedLine Citation:
PMID:  11230319     Owner:  NLM     Status:  MEDLINE    
Dahl salt-sensitive rats (DS), which have a mutation in the alpha-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 alpha-1 than alpha-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 alpha-1 Na(+)/K(+)-ATPase isoform). Unlike ouabain (IC(50)=248 micromol/L), serially diluted, HPLC-purified MBG immunoreactivity from DS and authentic MBG potently inhibited rat kidney Na(+)/K(+)-ATPase (IC(50)=70 and 78 nmol/L, respectively). Our results suggest that an alpha-1 Na(+)/K(+)-ATPase ligand, MBG, is elaborated to promote natriuresis in hypertensive DS. MBG acts as a selective inhibitor of the ouabain-resistant alpha-1 Na(+)/K(+)-ATPase subunit, ie, the major sodium pump isoform of the kidneys, as would be expected of a putative natriuretic hormone.
O V Fedorova; N I Kolodkin; N I Agalakova; E G Lakatta; A Y Bagrov
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Hypertension     Volume:  37     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-03-20     Completed Date:  2001-04-26     Revised Date:  2013-03-18    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  462-6     Citation Subset:  IM    
Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, Baltimore, Md, USA.
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MeSH Terms
Blood Pressure / drug effects
Bufanolides / blood,  isolation & purification,  metabolism*,  urine
Chromatography, High Pressure Liquid
Enzyme Inhibitors / metabolism
Hypertension / blood,  metabolism*,  urine
Isoenzymes / antagonists & inhibitors,  isolation & purification
Kidney / enzymology*
Ouabain / blood,  urine
Rats, Inbred Dahl
Sodium / blood
Sodium Chloride / administration & dosage
Sodium, Dietary / administration & dosage
Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors*,  isolation & purification
Reg. No./Substance:
0/Bufanolides; 0/Enzyme Inhibitors; 0/Isoenzymes; 0/Sodium, Dietary; 470-42-8/marinobufagenin; 630-60-4/Ouabain; 7440-23-5/Sodium; 7647-14-5/Sodium Chloride; EC ATPase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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