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      Effect of the Long-Term Treatment with Trandolapril on Endoglin Expression in Rats with Experimental Renal Fibrosis Induced by Renal Mass Reduction

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          Abstract

          Background: Endoglin is a membrane glycoprotein that regulates TGF-β1 signaling. Previous studies have revealed that endoglin is upregulated in several models of experimental fibrosis, and that endoglin expression can counteract the fibrogenic effects of TGF-β1. As treatment with angiotensin converting enzyme (ACE) inhibitors reduces renal fibrosis by mechanisms that are, in part, not dependent on angiotensin II blockade, we have assessed the hypothesis that this effect could be mediated by endoglin upregulation. Methods: We have used the 5/6-nephrectomy renal mass reduction (RMR) model of renal fibrosis in rats treated (RMR+T) or not treated with the ACE inhibitor trandolapril (0.7 mg/kg/day). One, 3 and 5 months after RMR, mean arterial pressure and renal function were measured. In addition, renal fibrosis was evaluated quantitatively and endoglin, TGF-β1, collagen type I and collagen type IV expression was assessed by Northern blot and immunohistochemistry. Results: RMR induced a progressive increase in mean arterial pressure, urinary protein excretion and glomerular and tubulointerstitial fibrosis, which is accompanied by an increased expression of TGF-β1, endoglin and collagen types I and IV. Trandolapril treatment reduced systemic blood pressure and lessened proteinuria after RMR, as well as expression of TGF-β1, endoglin and collagens. Conclusion: The present study demonstrates an increased TGF-β1, endoglin, collagen type I and collagen type IV expression in rats with severe hypertension and renal damage. The effect of trandolapril to decrease renal fibrosis seems to be based in a reduced TGF-β1 expression but not in an increased expression of endoglin.

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          Author and article information

          Journal
          KBR
          Kidney Blood Press Res
          10.1159/issn.1420-4096
          Kidney and Blood Pressure Research
          S. Karger AG
          1420-4096
          1423-0143
          2005
          December 2004
          11 January 2005
          : 28
          : 1
          : 32-40
          Affiliations
          aDepartamento de Fisiología y Farmacología, Instituto ‘Reina Sofía’ de Investigación Nefrológica, and bDepartamento de Anatomía e Histología Humanas, Universidad de Salamanca, Salamanca, Spain
          Article
          81439 Kidney Blood Press Res 2005;28:32–40
          10.1159/000081439
          15475654
          © 2005 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: 3, Tables: 2, References: 39, Pages: 9
          Product
          Self URI (application/pdf): https://www.karger.com/Article/Pdf/81439
          Categories
          Original Paper

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