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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      Effects of Aortic Stenosis on Renal Renin, Angiotensin Receptor, Endothelin and NOS Gene Expression in Rats

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          Abstract

          Background/Aims: Published data regarding the effects of common cardiovascular diseases, i.e. aortic stenosis on renal regulation of major vasoconstrictive (renin, endothelins) and vasodilatory systems (NO) are controversial. Therefore we aimed to evaluate the effects of chronic aortic stenosis on the renal renin-angiotensin, endothelin and NO systems. Methods: Experimental supravalvular aortic stenosis was induced by using silver clips with a 0.6 mm internal diameter on the ascending aorta of weanling rats. Renal endothelin-1 (ET-1), endothelin-3 (ET-3), renin, AT<sub>1a</sub>, AT<sub>1b</sub>, eNOS, and bNOS gene expression were assessed by RNase protection assay. Results: Renal renin gene expression increased twofold in rats with aortic stenosis. In contrast, renal ET-1, ET-3, eNOS, bNOS, and AT<sub>1a</sub>, AT<sub>1b</sub> gene expression were unchanged in rats with aortic stenosis. Conclusion: Our study demonstrates that in rats with severe experimental supravalvular aortic stenosis only renal renin gene expression is stimulated. This contrasts with severe heart failure where endothelins and NO synthases are also upregulated. Different patterns of regulation of renal vasoactive mediators may be of importance for the extent of the renal impairment associated with aortic stenosis, and may be correlated with the severity of congestive heart failure.

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          Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.

          A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described. The method provides a pure preparation of undegraded RNA in high yield and can be completed within 4 h. It is particularly useful for processing large numbers of samples and for isolation of RNA from minute quantities of cells or tissue samples.
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            Regulation of extracellular matrix proteins in pressure-overload cardiac hypertrophy: effects of angiotensin converting enzyme inhibition.

            Left ventricular hypertrophy (LVH) is characterized by remodeling of both myocyte and interstitial compartments of the heart. The aim of this investigation was to study the effects of angiotensin converting enzyme (ACE) inhibition on alterations in the composition of the interstitium in chronic pressure-overload hypertrophy.
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              Regulation of renin gene expression in kidneys of eNOS- and nNOS-deficient mice.

              Our study aimed to assess the roles of nitric oxide derived from endothelium NO-synthase (eNOS) and macula densa neuronal NO-synthase (nNOS) in the regulation of renal renin expression. For this purpose renin mRNA levels and renin content were determined in kidneys of wild-type (wt), nNOS-deficient (nNOS-/-), and eNOS-deficient (eNOS-/-) mice, in which the renin system was suppressed by feeding a high-salt diet (NaCl 4%), or was stimulated by feeding a low-salt (NaCl 0.02%) diet together with the converting-enzyme inhibitor ramipril (10 mg kg(-1) day(-1)). In all mouse strains, renin mRNA levels were inversely related to the rate of sodium intake. In eNOS-/- mice renin mRNA levels and renal renin content were 50% lower than in wt mice at each level of salt intake, whilst in nNOS-/- mice renin expression was not different from wt controls. Administration of the general NO-synthase inhibitor nitro-L-arginine methyl ester (L-NAME, 50 mg kg(-1) day(-1)) to mice kept on the low-salt/ramipril regimen caused a decrease of renal renin mRNA levels in wt and nNOS-/- mice, but not in eNOS-/- mice. These observations suggest that neither eNOS nor nNOS is essential for up- or downregulation of renin expression. eNOS-derived NO appears to enhance renin expression, whereas nNOS-derived NO does not.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2002
                February 2002
                28 March 2002
                : 22
                : 1
                : 84-89
                Affiliations
                aKlinik und Poliklinik für Innere Medizin II, University of Regensburg, und bInstitut für Klinische Pharmakologie und Toxikologie, Freie Universität Berlin, Deutschland
                Article
                46679 Am J Nephrol 2002;22:84–89
                10.1159/000046679
                11919408
                8039ed68-6415-4ebb-bae0-c24c36bcbd47
                © 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.

                History
                Page count
                Figures: 1, Tables: 1, References: 38, Pages: 6
                Categories
                Laboratory Investigation

                Cardiovascular Medicine,Nephrology
                Renin regulation,Renal renin,Renal bNOS,Renal eNOS,Experimental supravalvular aortic stenosis,Renal endothelin-3,Congestive heart failure,Renal endothelin-1

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