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      Mechanism of Acetazolamide-Induced Rise in Renal Vascular Resistance Assessed in the Dog Whole Kidney

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          Abstract

          The reduction in renal blood flow (RBF) and glomerular filtration rate (GFR) observed after the administration of the carbonic anhydrase inhibitors acetazolamide and benzolamide had been explained as due to activation of the tubuloglomerular feedback mechanism. If correct, pharmacologic blockade of this pathway should prevent the development of renal vasoconstriction with the carbonic anhydrase inhibitors. Thus, the current study evaluates in the dog whole kidney the effect of acetazolamide (20 mg/ kg body weight) in the presence or absence of furosemide (5 mg/kg body weight), a drug which blocks the tubuloglomerular feedback. Acetazolamide resulted in a large increase in urinary bicarbonate excretion accompanied by a significant reduction in GFR (16%) and RBF (18%). By contrast with the effects of acetazolamide, furosemide did not alter GFR and increased RBF. In addition, the loop diuretic induced a large chloruresis without changes in urinary bicarbonate excretion. The infusion of acetazolamide in furosemide-treated dogs resulted in a significant increment in renal bicarbonate excretion and in a significant reduction in the levels of both GFR (28%) and RBF (13%). Therefore, furosemide pretreatment did not block the effects of acetazolamide on renal hemodynamic parameters. Consequently, the acetazolamide-induced reduction in both GFR and RBF cannot ba accounted for by changes in chloride levels in the juxtaglomerular region due to enhanced salt transport in the macula densa/distal nephron. The increased renal vascular resistance observed with acetazolamide might occur by either a direct effect of this agent on the renal circulation or as a result of changes in intrarenal pressure secondary to the inhibition of proximal fluid reabsorption.

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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
          1992
          1992
          07 November 2008
          : 15
          : 2
          : 99-105
          Affiliations
          aRenal Section, Hospital de Clinicas, Universidad de Buenos Aires, Argentina bDepartment of Medicine, Baylor College of Medicine, Divison of Nephrology, Veterans Affairs Medical Center, Houston, Tex., USA
          Article
          173447 Renal Physiol Biochem 1992;15:99–105
          10.1159/000173447
          1375769
          © 1992 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: 7
          Categories
          Original Paper

          Cardiovascular Medicine, Nephrology

          Acetazolamide, Tubuloglomerular feedback, Renal circulation

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