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      Has the Elusive ‘Natriuretic Factor’ Been Discovered, and If So, Is It a Hormone?

      ,

      Cardiorenal Medicine

      S. Karger AG

      Natriuresis, Ouabain-like factor, Na+/K+-ATPase, Vasoreactivity, LLU-α, HIF, HHIF, OLF

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          Abstract

          This review summarizes the interesting and significant papers reported at the International Conference on Natriuretic and Digitalis-like Factors held at the ASH meeting in San Francisco, June 1–2, 1997. This area of investigation has been rejuvenated as of late with near structural determination of two ouabain-like isolates from human plasma (OLF) and bovine hypothalamus (HIF) which are apparently the same compound and the isolation and structural elucidation of a natriuretic metabolite of γ-tocopherol. Spectroscopic information has also been obtained for two other compounds, an ouabain-like factor from bovine adrenals and HHIF from the hypothalamus. An explanation was offered for how low concentrations of digitalis-like factors can regulate vascular reactivity when the predominant isoform of the sodium pump has a low affinity for these compounds. Various groups are examining possible in vivo synthetic pathways that could lead to the production digitalis-like factors. The natriuretic metabolite of γ-tocopherol, LLU-α, fits deWardener’s postulates for a natriuretic hormone and is being examined for its involvement in ECF control. Once the structures for some of these ouabain-like compounds are determined and they are synthesized, these compounds will also be able to be studied employing classical pharmacologic methods.

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          Most cited references 3

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          A new endogenous natriuretic factor: LLU-alpha.

          For over three decades, renal physiology has sought a putative natriuretic hormone (third factor) that might control the body's pool of extracellular fluid, an important determinant in hypertension, congestive heart failure, and cirrhosis. In our search for this hormone, we have isolated several pure natriuretic factors from human uremic urine that would appear, alone or in combination, to mark a cluster of phenomena previously presumed to be that of a single "natriuretic hormone." This paper reports the purification, chemical structure, and total synthesis of the first of these compounds, LLU-alpha, which proved to be 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman, presumably a metabolite of gamma-tocopherol. Both natural LLU-alpha and synthetic material are identical (except for optical activity) with respect to structure and biological activity. It appears that the natriuretic activity of LLU-alpha is mediated by inhibition of the 70 pS K+ channel in the apical membrane of the thick ascending limb of the kidney.
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            Natriuretic hormone--the missing link in low renin hypertension?

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              Endogenous natriuretic factors 1: Sodium pump inhibition does not correlate with natriuretic or pressor activities from uremic urine

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                Author and article information

                Journal
                EXN
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                1660-2129
                1998
                December 1998
                06 November 1998
                : 6
                : 6
                : 488-490
                Affiliations
                Laboratory of Chemical Endocrinology, Loma Linda University, Loma Linda, Calif., USA
                Article
                20561 Exp Nephrol 1998;6:488–490
                10.1159/000020561
                © 1998 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 1, References: 12, Pages: 3
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/20561
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