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      Prepubertal Treatment with Angiotensin Receptor Blocker Causes Partial Attenuation of Hypertension and Renal Damage in Adult Dahl Salt-Sensitive Rats

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          Abstract

          Recently, we have shown that treatment of stroke-prone spontaneously hypertensive rats with angiotensin inhibitors for a limited time-window before puberty results in an attenuation of hypertensive nephrosclerosis in later life. The aim of this study was to examine the applicability of this therapeutic paradigm to a low-renin model. Dahl salt-sensitive (Dahl-S) rats were fed a high-salt diet from age 6 weeks. Some rats were treated with the angiotensin receptor blocker (ARB) candesartan cilexetil (2 mg/kg/d) from weaning to puberty (age 3–10 weeks), whereas other rats were treated continuously until overt renal damage was seen (age 3–16 weeks). Dahl-S rats on a high salt diet had increased blood pressure (207 ± 3 vs. 125 ± 2 mm Hg), proteinuria, and glomerular/vascular histological changes. The prepubertal treatment with ARB resulted in a continued suppression of blood pressure (153 ± 2 mm Hg) at 16 weeks. Both proteinuria and renal histological changes were significantly (p < 0.05) attenuated, but not completely prevented by the treatment. No significant differences in plasma renin activity, renin mRNA, or AT1/AT2 mRNA were seen between groups. These results suggest that prepubertal treatment affords sustained renoprotection, even in an animal model with a suppressed renin-angiotensin system, and support the notion that appropriate prepubertal intervention may lead to a partial attenuation in the susceptibility to inherited renal diseases.

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          Most cited references 1

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          The debate on the ‘amplifier hypothesis’ - some comments

           Björn Folkow (2000)
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            Author and article information

            Journal
            NEF
            Nephron
            10.1159/issn.1660-8151
            Nephron
            S. Karger AG
            1660-8151
            2235-3186
            2002
            August 2002
            15 July 2002
            : 91
            : 4
            : 710-718
            Affiliations
            Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan
            Article
            65035 Nephron 2002;91:710–718
            10.1159/000065035
            12138277
            © 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: 6, Tables: 1, References: 21, Pages: 9
            Product
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/65035
            Categories
            Original Paper

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