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      Coronary β-Adrenoceptor Function Is Modified by the Endothelium in Heart Failure


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          Congestive heart failure is associated with abnormalities in myocardial β-adrenoceptor function. The extent of vascular β-adrenoceptor alterations at heart failure, however, is unknown. Accordingly, we examined β-adrenoceptor-mediated relaxations in both circumflex (CRX) and left anterior descending (LAD) coronary arteries with and without endothelium from dogs in early and end-stage heart failure induced by rapid ventricular pacing (1 and 4 weeks pacing at 250 beats·mkr<sup>1</sup>, respectively). At early heart failure, (1) CRX with endothelium were more sensitive to isoproterenol than CRX without endothelium (EC<sub>50</sub>: 1.1 × 10<sup>–8</sup> vs. 1.6 × 10<sup>–7</sup> M, p < 0.05); and (2) in response to salbutamol, CRX with endothelium had a lower maximum relaxation response than CRX without endothelium (56.6 vs. 75.9%, p < 0.05). At end-stage heart failure, (1) endothelium-intact CRX and LAD showed a significant decrease in sensitivity to isoproterenol compared to control (CRX- EC<sub>50:</sub> end-stage heart failure: 1.1 × 10<sup>–7</sup> vs. control: 1.8 × 10<sup>–8</sup> M, p < 0.05; and LAD-EC<sub>50</sub>: end-stage heart failure: 8.8 × 10<sup>–7</sup> M vs. control: 8.3 × 10<sup>-8</sup> M, p < 0.05); (2) LAD with endothelium showed greater maximum relaxation to salbutamol than LAD without endothelium (100.8 vs. 76.5%, p < 0.05); and (3) CRX were significantly more sensitive to isoproterenol than LAD. These data suggest that coronary vascular tone via β-adrenoceptor stimulation is coronary artery-dependent, and modulated not only by the heart failure state, but also by the presence of a functional endothelium.

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          Author and article information

          J Vasc Res
          Journal of Vascular Research
          S. Karger AG
          24 September 2008
          : 33
          : 1
          : 62-70
          Division of Cardiology, St. Michael’s Hospital, and Department of Pharmacology, University of Toronto, Toronto, Canada
          159133 J Vasc Res 1996;33:62–70
          © 1996 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.

          : 08 February 1995
          : 20 July 1995
          Page count
          Pages: 9
          Research Paper

          General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
          Coronary arteries, canine,Isoproterenol,Congestive heart failure,β-Adrenoceptors,Endothelium


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