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      Effects of an Angiotensin II Receptor Antagonist on the Progression of Renal Failure in Hyperlipidemic Imai Rats

      ,

      Nephron

      S. Karger AG

      Spontaneous proteinuria, Angiotensin II receptor antagonist, DuP 753, Glomerulosclerosis

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          Abstract

          This study was undertaken to determine the role of angiotensin II (AII) in the development of glomerulosclerosis, using an AII receptor antagonist in an animal model of hyperlipidemia. Hyperlipidemic Imai rats were employed because they spontaneously develop glomerulosclerosis; this is especially true in males. Group 1 (n = 5) received no specific therapy. Group 2 (n = 5) was treated with enalapril at a dosage of 50 mg/l in drinking water starting at 6 weeks of age. Group 3 (n = 5) and group 4 (n = 6) were treated with the AII receptor antagonist DuP 753 at a respective dosage of 15 mg/l (low-dose DuP) and 150 mg/l (high-dose DuP) in drinking water. Body weight, blood pressure, urinary protein, serum albumin, cholesterol, BUN and serum creatinine were measured and compared among the groups from 12 to 24 weeks of age. Enalapril and high-dose DuP were almost equally effective in controlling systemic hypertension. Each treatment significantly reduced proteinuria (172 + 112 and 152 ± 72 mg/kg/day at 24 weeks) as compared with that in the controls (421 ± 147 mg/kg/day; p < 0.05 and p < 0.0l, respectively). Hypercholesterolemia also decreased (82 ± 4 and 89 ± 6 mg/dl) as compared with that of the controls (141 ± 48 mg/dl; both p < 0.05). Glomerulosclerosis index (SI) was significantly higher in the untreated control rats (55 ± 26) than in the enalapril-treated rats (2 ± 3; p < 0.005) and the high-dose-DuP-treated rats (6 ± 6, p < 0.005). Low-dose-DuP-treated rats showed lower proteinuria (217 ± 83 vs. 421 ± 147 mg/kg/ day; p < 0.05) and a lower SI (19 ± 5 vs. 55 ± 26; p < 0.01) than did the untreated control rats, although there was no significant difference in systemic hypertension between the two groups. These results, which show a sharp contrast between the effects of an AII receptor antagonist on blood pressure and renal injury, suggest that AII is involved in the development of glomerulosclerosis even in hyperlipidemic Imai rats.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1993
          1993
          12 December 2008
          : 65
          : 3
          : 426-432
          Affiliations
          Department of Internal Medicine, Saga Medical School, Saga, Japan
          Article
          187524 Nephron 1993;65:426–432
          10.1159/000187524
          8289994
          © 1993 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

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