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      Chronic Inhibition of Nitric Oxide Synthase in Heymann Nephritis

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          Abstract

          Effects of nitric oxide (NO) synthase inhibition on blood pressure and on the course of Heymann nephritis was examined in rats. L-N<sup>G</sup>-nitroarginine-methylester ( L-NAME, 10 mg/l00 ml in the drinking water for 12 weeks) was used as an inhibitor of NO synthase. Urinary excretion of guanosine 3’,5’-cyclic monophosphate (cGMP), a second messenger of NO, was used as an indirect estimate of NO activity. Rats were divided into the following groups: control, nephritis, L-NAME, and nephritis- L-NAME. Urinary cGMP excretion was lower in the nephritis group (p < 0.05) and in the nephritis- L-NAME group (p < 0.005) compared with controls. Plasma atrial natriuretic peptide (ANP) levels were elevated in the nephritis (p < 0.001) and in the nephritis- L-NAME groups (p < 0.05). L-NAME treatment alone did not have any effect on plasma ANP levels. Blood pressure rose progressively in all L-NAME-treated rats. Most marked albuminuria developed in the nephritis- L-NAME group. No differences in the immunohistological findings were observed between the nephritis and the nephritis- L-NAME groups. NO synthase inhibition causes hypertension and aggravates albuminuria in chronic nephritis. Moreover, nephritis itself may decrease the production of cGMP either as a consequence of blunted NO activity or, in addition, because of ANP resistance. It appears that NO synthase inhibition does not change the immunological course of Heymann nephritis but rather the increased hemodynamic load makes the course of nephritis worse.

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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
          24 December 2008
          : 74
          : 1
          : 144-149
          Affiliations
          aMinerva Foundation Institute for Medical Research, bFourth Department of Medicine, Helsinki University Central Hospital, cDepartment of Bacteriology and Immunology, University of Helsinki, Finland
          Article
          189294 Nephron 1996;74:144-149
          10.1159/000189294
          8883033
          33102d22-b75b-4057-968f-ddb3b5125ead
          © 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.

          History
          : 20 October 1995
          Page count
          Pages: 6
          Categories
          Original Paper

          Cardiovascular Medicine,Nephrology
          Nitric oxide,Nephritis,Hypertension,Urinary cGMP,Atrial natriuretic peptide

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