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      Distinct Role of Intrarenal Cyclooxygenase-1/2 in Chronic Unilateral Renal Ischemia

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          Abstract

          Aims: The role of cyclooxygenase (COX)-1/2-induced prostaglandins (PG) in unilateral chronic renal ischemia of anesthetized dogs was examined. Methods: Ischemic kidneys were established by reducing renal blood flow of left renal artery to 10% of baseline with an adjustable clip. After 4 weeks, changes in intrarenal contents of PGE2/PGI2 and angiotensin (Ang) II were evaluated with renal microdialysis and biopsy. Furthermore, the effect of a non-specific COX inhibitor (sulpyrine), a COX-2-specific inhibitor (NS398), and an Ang receptor antagonist (CS866) on renal function and renal PG contents were evaluated. Results: Unilateral renal artery clipping reduced renal plasma flow (RPF) in clipped (from 59 ± 2 to 17 ± 1 ml/min, n = 18) and nonclipped kidneys (from 59 ± 2 to 44 ± 2 ml/min) and natriuresis. Intrarenal PGE2 increased only in clipped kidneys (from 114 ± 7 to 375 ± 25 pg/ml), whereas 6-keto-PGF1α increased in both kidneys. Sulpyrine reduced intrarenal PG contents, and decreased RPF, GFR, and urinary sodium excretion (UNaV), whereas NS398 reduced UNaV in clipped (from 4.0 ± 0.9 to 1.7 ± 0.2 µEq/min) and nonclipped kidneys (from 5.4 ± 0.5 to 2.9 ± 0.3 µEq/min), without affecting renal hemodynamics. Intrarenal Ang II contents increased in clipped (from 0.70 ± 0.06 to 2.32 ± 0.33 pg/mg, n = 18) and nonclipped kidneys (from 0.65 ± 0.06 to 2.45 ± 0.33 pg/mg, n = 18), and CS866 improved renal hemodynamics and natriuresis. The elevated intrarenal Ang II content was suppressed by NS398 only in clipped kidneys. Conclusion: Unilateral renal ischemia elevates intrarenal PGE2 contents in clipped kidneys, which serves to countervail the aggravation of renal function. Furthermore, intrarenal COX isoforms may play differential roles, with COX-1 participating in modulation of renal hemodynamics, and COX-2 contributing to sodium excretion and Ang II formation.

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          Rapid extraction of oxygenated metabolites of arachidonic acid from biological samples using octadecylsilyl silica

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            Ischemic renal disease

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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
              September 2002
              14 August 2002
              : 92
              : 1
              : 183-191
              Affiliations
              Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan
              Article
              64479 Nephron 2002;92:183–191
              10.1159/000064479
              12187101
              © 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, References: 35, Pages: 9
              Product
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/64479
              Categories
              Original Paper

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