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      Ontogenic Expression of Renal and Hepatic Angiotensin II Receptor Genes in the Rat

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          Abstract

          In addition to its well-characterized renal hemodynamic effects, angiotensin II (Ang II) promotes growth of cultured glomerular and tubular cells, suggesting a possible role in renal development. To better define potential developmental effects of Ang II, we examined the expression of Ang II receptors in embryonic (E19) and postnatal (1, 2, 3, 10 days, 6 weeks, 3 and 9 months) rat kidneys, using in situ autoradiography and the nonpeptide antagonists losartan and PD-123177 to identify receptor subtypes. At E19, <sup>125</sup>I-[Sar<sup>1</sup>, Ile<sup>8</sup>]Ang II binding was equally reduced by losartan and PD-123177, indicating the presence of both AT<sub>1</sub> and AT<sub>2</sub> receptors. A progressive increase in Ang II receptor density occurred after birth, reaching a plateau at day 10. At that time, the AT<sub>1</sub> subtype predominated and was virtually the sole subtype present thereafter. Ang II receptor density and AT<sub>1</sub> mRNA levels decreased in aging rats. Total AT<sub>1</sub> receptor mRNA levels in both kidney and liver were determined by Northern hybridization analysis using a radiolabeled AT<sub>1</sub> anti-sense cRNA probe. In both tissues, AT<sub>1</sub> mRNA levels increased rapidly following birth, reached a maximum on day 10 and decreased thereafter. To further characterize the ontogenic effects on AT<sub>1</sub> gene expression, renal AT<sub>1A</sub> and AT<sub>1B</sub> receptor mRNA isoforms were determined by reverse transcription and the polymerase chain reaction. No significant differences were observed during maturation between the relative levels of AT<sub>1A</sub> and AT<sub>1B</sub> mRNAs, with the AT<sub>1A</sub> isoform accounting for approximately 78% at any time point. Thus, renal AT<sub>1</sub> receptor density increases rapidly after birth, in association with an increase in both AT<sub>1A</sub> and AT<sub>1B</sub> receptor gene expression. As the predominant receptor isoform in the adult kidney, the AT<sub>1A</sub> receptor may account for the majority of the effects of Ang II on glomerular and tubular function.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1997
          1997
          23 December 2008
          : 76
          : 1
          : 103-110
          Affiliations
          aDivision of Endocrinology, San Francisco General Hospital, University of California San Francisco, Calif, USA, and bHypertension Unit, Department of Internal Medicine, University of Udine, Italy
          Article
          190148 Nephron 1997;76:103–110
          10.1159/000190148
          9171308
          © 1997 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: 8
          Categories
          Original Paper

          Cardiovascular Medicine, Nephrology

          Kidney, Losartan, AT1 mRNA, PD-123177, Liver

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