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      Does Aldosterone-lnduced Cardiac Fibrosis Involve Direct Effects on Cardiac Fibroblasts?


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          To investigate the hypothesis that aldosterone plays a role in the development of fibrosis, cultured fibroblasts from adult rat heart have been examined for their expression of aldosterone receptors and the effects of aldosterone on collagen synthesis. Binding assays with both <sup>3</sup>H-aldosterone and <sup>3</sup>H-RU26752 in intact cardiac fibroblasts and cytosolic extracts from cardiac fibroblasts failed to reveal expression of aldosterone receptors. However, using the method of reverse transcription-polymerase chain reaction, we could demonstrate the expression of mRNA for the mineralocorticoid receptor in both cardiac fibroblasts and neonatal rat cardiomyocytes. Functional studies investigating the effect of aldosterone on collagen synthesis (<sup>3</sup>H-proline incorporation into collagenous protein) revealed that aldosterone does not stimulate collagen synthesis in cardiac fibroblasts at concentrations (10<sup>–8</sup> to 10<sup>–9</sup> M) observed in primary or secondary hyperaldosteronism. At higher concentrations (10<sup>–6</sup> to 10<sup>-7</sup> M) aldosterone inhibited collagen synthesis. Expression of collagen genes Iα1, IIlα1, IVα1 and of the collagenase gene was not affected by aldosterone. The collagen gene VIα2 was also found to be expressed in cultured cardiac fibroblasts, and its expression was also independent of aldosterone. The data indicate that fibrosis is not due to a direct effect of aldosterone on fibroblast collagen synthesis.

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          Author and article information

          J Vasc Res
          Journal of Vascular Research
          S. Karger AG
          24 September 2008
          : 33
          : 4
          : 315-326
          aDepartment of Research, Cardiophysiology, University Hospital, Basel, bDivision of Cardiology, Kantonsspital, Lucerne, Switzerland
          159159 J Vasc Res 1996;33:315–326
          © 1996 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.

          : 10 November 1995
          : 09 February 1996
          Page count
          Pages: 12
          Research Paper

          General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
          Aldosterone,Fibrosis,Collagen expression,Mineralocorticoid receptor mRNA,Cardiac fibroblasts


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