| Marinobufagenin, an endogenous alpha-1 sodium pump ligand, in hypertensive Dahl salt-sensitive rats. | |
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MedLine Citation:
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PMID: 11230319 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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O V Fedorova; N I Kolodkin; N I Agalakova; E G Lakatta; A Y Bagrov |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Hypertension Volume: 37 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2001 Feb |
Date Detail:
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Created Date: 2001-03-20 Completed Date: 2001-04-26 Revised Date: 2013-03-18 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 462-6 Citation Subset: IM |
Affiliation:
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Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, Baltimore, Md, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals 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* Natriuresis Ouabain / blood, urine Rats Rats, Inbred Dahl Sodium / blood Sodium Chloride / administration & dosage Sodium, Dietary / administration & dosage Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors*, isolation & purification |
| Chemical | |
Reg. No./Substance:
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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 3.6.3.9/Sodium-Potassium-Exchanging ATPase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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