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      Generation of Nitric Oxide from Organic Nitrovasodilators during Passage through the Coronary Vascular Bed and Its Role in Coronary Vasodilation and Nitrate Tolerance

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          Abstract

          This study investigated the release of nitric oxide (NO) from glyceryl trinitrate (GTN) and SIN-1 in Langendorff rabbit hearts. Infusion of either GTN (10–40µ M) or SIN-1 (0.45–4.5 µ M) into the coronary inflow tract resulted in a decrease in coronary perfusion pressure and NO release (oxyhemoglobin technique) into the coronary effluent. NO release fom SIN-1 occurred spontaneously whereas passage through the coronary circulation, i.e. active metabolism, was required for NO release from GTN. Removal of the coronary endothelium and blockade of endothelial NO formation did not affect NO release from GTN and SIN-1. In GTN-tolerant hearts, there was a considerable inhibition of GTN- but not SIN-1-induced NO formation and coronary vasodilation. These data suggest (1) that metabolic NO release from GTN occurs during passage of the coronary circulation and is independent of the presence of endothelium, and (2) reduced NO release is a major cause of nitrate tolerance.

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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
          978-3-8055-5380-3
          978-3-318-01726-7
          1018-1172
          1423-0135
          1991
          1991
          23 September 2008
          : 28
          : 1-3
          : 62-66
          Affiliations
          Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, BRD
          Article
          158844 Blood Vessels 1991;28:62–66
          10.1159/000158844
          © 1991 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: 5
          Categories
          Endothelium-Derived and Endothelium-Independent Vasoactive Mechanisms

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