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      Endothelin Does Not Contribute to the Attenuation in Myocardial Function and Blood Flow after Repetitive Ischemia in the Rat Heart

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          Abstract

          An increased release of the potent vasoconstrictor endothelin (ET) may play a role in the development of myocardial stunning. We, therefore, hypothesized that blockade of ET with either monoclonal antibodies against ET-1 and ET-3 (a-ETl/3-ab) or with the ET<sub>a</sub> receptor antagonist BQ123 would improve the reduction in myocardial blood flow (MBF; H<sub>2</sub> clearance) and fractional wall thickening (FT; pulsed Doppler) after repetitive ischemia/reperfusion in an in situ perfused rat model. Under baseline conditions, ET-1 dose dependently decreased MBF and increased mean arterial blood pessure. FT and heart rate were unaltered. Pretreatment with both a-ETl/3-ab or BQ123 effectively blocked the effects of ET. Following repetitive ischemia, MBF was significantly reduced from 3.5 ± 0.4 to 2.1 ± 0.3 ml × min<sup>–1</sup> × g<sup>–1</sup> (p& < 0.05) and FT from 16.2 ± 1.7 to 9.4 ± 1.1% in the control group (p& < 0.05). Pretreatment with either antibodies did not significantly improve the attenuation in MBF and FT at the end of the ischemic protocol. These results indicate that inhibition of ET-1 by monoclonal antibodies or by ET<sub>A</sub> receptor blockade does not influence the decrease in MBF and FT in repetitive ischemia/reperfusion. We, therefore, propose that ET is not a major determinant in the development of myocardial stunning.

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          Author and article information

          Journal
          JVR
          J Vasc Res
          10.1159/issn.1018-1172
          Journal of Vascular Research
          S. Karger AG
          1018-1172
          1423-0135
          1997
          1997
          24 September 2008
          : 34
          : 6
          : 447-454
          Affiliations
          aDepartment of Cardiology, University of Heidelberg, Germany; bDepartment of Cardiology, University of Glasgow, UK
          Article
          159255 J Vasc Res 1997;34:447–454
          10.1159/000159255
          9425997
          c29a9e41-4017-4295-8eae-9c2c785635fd
          © 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.

          History
          : 20 March 1997
          : 27 June 1997
          Page count
          Pages: 8
          Categories
          Research Paper

          General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
          Myocardial blood flow,ETA receptor antagonist,Monoclonal endothelin antibodies,Endothelin,Fractional wall thickening,Myocardial stunning

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