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      Renoprotective Mechanisms of Angiotensin II Antagonism in Experimental Chronic Renal Failure

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          Abstract

          Aims: We investigated angiotensin II and nitric oxide-cGMP pathway in the development of hypertension and renal damage in chronic experimental nephritis. Methods: Rats with autoimmune nephritis were treated for 12 weeks with AT1 receptor antagonist L-158,809 and/or ACE inhibitor captopril given in drinking water. Blood pressure, urinary albumin, and urinary excretion of cGMP were measured. Renal density of ACE, AT1 and AT2 receptors was determined by quantitative in vitro autoradiography. Results: L-158,809, captopril, and their combination decreased blood pressure and normalised urinary albumin excretion rate in rats with nephritis. In L-158,809-treated rats, cGMP excretion was increased compared to the vehicle-treated nephritic group suggesting that the dysfunctional nitric oxide system may be activated by angiotensin antagonism. In nephritic rats, AT1 and AT2 receptor binding densities in renal medulla were decreased, cortical AT receptor expression remained unchanged. Following L-158,809 treatment, both AT1 and AT2 receptor binding was suppressed. Conclusion: Long-term blockade of AT1 receptors in chronic nephritis has beneficial effects both on albuminuria and blood pressure being as effective as ACE inhibition or their combination. The stimulatory effect of AT1 receptor antagonism on cGMP production was not mediated by AT2 receptor-dependent mechanisms suggesting that AT1 receptor blockade per se favours activation of humoral pathways that stimulate cGMP production and potentially contribute to renal protection in chronic nephritis.

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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
          2002
          2002
          03 July 2002
          : 25
          : 2
          : 71-79
          Affiliations
          aMinerva Foundation Institute for Medical Research; bDepartment of Bacteriology and Immunology, Haartman Institute, University of Helsinki; cDepartment of Physiology, University of Oulu; dDepartment of Medicine, Helsinki University Central Hospital, Helsinki, Finland
          Article
          63511 Kidney Blood Press Res 2002;25:71–79
          10.1159/000063511
          12077487
          © 2002 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: 5, References: 36, Pages: 9
          Product
          Self URI (application/pdf): https://www.karger.com/Article/Pdf/63511
          Categories
          Original Paper

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