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      Effect of a Specific Endothelin Receptor A Antagonist on Glomerulonephritis of ddY Mice with IgA Nephropathy

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          Abstract

          The present study assessed renal endothelin (ET)-l ET-3, and ET receptor A and B mRNA levels in ddY mice at 8, 40, and 60 weeks of age. The renal mRNA levels of ET-1 increased significantly in ddY mice as their nephritis progressed, reaching a 6.6-fold (p < 0.01) higher level by 60 weeks than in control ICR mice. Renal ET-3 mRNA levels, however, remained unchanged. The renal mRNA levels of ET receptor A and B in ddY mice increased gradually with the progression of nephritis, reaching 4.8- (p < 0.01) and 3.6-fold (p < 0.01) higher levels, respectively, at 60 weeks of age than found in control ICR mice. A positive correlation was noted between ET-1 and ET receptor mRNA levels and histopathological changes in renal tissues. In addition, we assessed whether a specific ET receptor A antagonist, FR139317, affects the progression of glomerulonephritis in ddY mice. At 24 weeks of age (before glomerulonephritis developed), ddY mice were divided into two groups that received mtraperitoneally either FR139317 or its vehicle (saline) daily for 36 weeks. The development of histopathological lesions and urinary protein excretion were suppressed by FR139317 treatment. These data suggest that ET families play a role in the progression of glomerulonephritis and that FR139317 treatment can be used therapeutically in ddY mice with IgA nephropathy.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1996
          1996
          18 December 2008
          : 72
          : 3
          : 454-460
          Affiliations
          Division of Nephrology, Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan
          Article
          188912 Nephron 1996;72:454–460
          10.1159/000188912
          8852496
          © 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.

          Page count
          Pages: 7
          Categories
          Original Paper

          Cardiovascular Medicine, Nephrology

          Extracellular matrix, Endothelin receptor, Endothelin-1, mRNA

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