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      Effect of Tropolone on Vascular Sympathetic Neuroeffector Transmission

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          Abstract

          After a latency period the catechol- O-methyltransferase inhibitor tropolone blocked increasingly the contractile response of rabbit isolated pulmonary artery elicited by electrical-field stimulation. Furthermore, tropolone contracted the artery. These inhibition effects were irreversible. In contrast, phentolamine caused a reversible equilibrium block with a rapid onset. Tropolone, which had been subjected to oxygenated physiological salt solution at 37 °C for a prolonged period, accelerated the development of neurogenic block compared to a freshly prepared solution of tropolone. This suggests that the blocking effect may in part be due to a break-down product of tropolone. Tropolone did not alter the electrical-field stimulation induced outflow of tritium from the pulmonary artery preloaded with <sup>3</sup>H-noradrenaline. Initially, tropolone did not alter the cumulative concentration-contraction response curves of exogenous noradrenaline, acetylcholine and serotonin. However, after prolonged exposure of the pulmonary artery to tropolone, this agent inhibited the response elicited by these agonists in an apparent noncompetitive manner. The results suggest that tropolone exerts a direct blocking effect on vascular smooth muscle, which probably is neither mediated through adrenergic receptors nor due to its catechol- O-methyltransferase inhibitory activity. The observed non-specific effects of tropolone must be taken into account when tropolone is employed as an enzyme inhibitor.

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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
          1974
          1974
          18 September 2008
          : 11
          : 3
          : 159-171
          Affiliations
          Institute of Pharmacology, University of Odense, Odense
          Article
          158009 Blood Vessels 1974;11:159–171
          10.1159/000158009
          © 1974 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: 13
          Categories
          Research Paper

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