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      Long–Term Effect on Blood Pressure of Early Brief Treatment by Different Antihypertensive Agents: A Study in the Prague Hypertensive Rat

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          Abstract

          In the Prague hypertensive rat (PHR), a strain of genetic hypertension derived from Wistar, administration of various antihypertensive drugs (AHD) during the developmental phase of hypertension (weeks 5–9 of life) prevents the rise of blood pressure. However, only drugs blocking the renin–angiotensin system (RAS, i.e. AT1–antagonist losartan and ACE inhibitor perindopril) have a long–term effect on blood pressure leading to values of systolic blood pressure (SBP) of 174.5±14.5 and 169.8±15.3 mmHg, respectively, at week 30. At this time, control, untreated PHR have a SBP of 222.0±16.6 mmHg (p<0.01 for both groups); age–matched PNR (Prague normotensive rat, bred in parallel with PHR from the same parent pair) exhibit values as low as 123.3±11.7 mmHg (p<0.01 from all other values). When losartan was administered to another group of PHR not only at weeks 5–9 but once more at weeks of 15–19 of age, the values of their SBP at week 30 were 156.8±12.64 mmHg, i.e., values significantly (p<0.01) different not only from 239.7±17.59 mmHg (value of the untreated PHR group) but also from 174.5±14.5 mmHg (value of PHR to which losartan was administered only once, at weeks 5–9). Thus, twice repeated administration of losartan in young age almost normalizes blood pressure deep into adult age. Proteinuria, a common finding in adult PHR, is also significantly lower in adult age in both groups receiving at weeks 5–9 drugs blocking RAS; the values at week 30 are 4.0±0.26 mg/24 h/rat in the losartan and 3.87±0.27 in the perindopril group, in contrast to 12.8±1.08 (p<0.01 for both groups) in control PHR. In conclusion, early brief administration (weeks 5–9 of life) of RAS–blocking agents to PHR led to long–term antihypertensive and antiproteinuric effects. These effects were significantly intensified by a second brief administration at weeks 15–19.

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          Long-term inhibition of the renin-angiotensin system in genetic hypertension

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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
            1998
            1998
            06 February 1999
            : 21
            : 6
            : 445-451
            Affiliations
            Department of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
            Article
            25898 Kidney Blood Press Res 1998;21:445–451
            10.1159/000025898
            9933830
            © 1998 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: 20, Pages: 7
            Product
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/25898
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            Original Paper

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