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      Inhibitors of Actin Filament Polymerisation Attenuate Force but Not Global Intracellular Calcium in Isolated Pressurised Resistance Arteries

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          Abstract

          Receptor-coupled contractile activation of arterial smooth muscle involves increases in intracellular calcium ([Ca<sup>2+</sup>]<sub>i</sub>) and subsequent alteration of myosin light chain phosphorylation. An additional mechanism whereby agonists could regulate vascular contractility may be alteration of actin filament dynamics. Therefore, in this study, we have investigated the influence of two inhibitors of actin filament polymerisation, cytochalasin D and latrunculin B, on the [Ca<sup>2+</sup>]<sub>i</sub> and force responsiveness of pressurised rat mesenteric arteries to α-adrenergic stimulation. Following cytochalasin D or latrunculin B treatment, phenylephrine-induced constrictions were significantly reduced to 11 ± 3.2% (n = 6) and 10 ± 4.4% (n = 6) of control, respectively, whereas [Ca<sup>2+</sup>]<sub>i</sub> remained at 98 ± 21% and 104 ± 7.0% of control, respectively. Such effects of cytochalasin D were not restricted to mesenteric small arteries. Cytochalasin D also significantly reduced the force, but not [Ca<sup>2+</sup>]<sub>i</sub> responses to agonist stimulation in other vascular (portal vein) and non-vascular (uterine) tissues. These data indicate that inhibitors of net actin polymerisation attenuate maximum agonist-induced force responsiveness without similar reductions in [Ca<sup>2+</sup>]<sub>i</sub> in pressurised resistance vessels and other smooth muscle tissues. This suggests that modulation of the dynamic equilibrium between filamentous F-actin and monomeric globular actin (G-actin) may be an important mechanism, acting independently of global [Ca<sup>2+</sup>]<sub>i</sub> homeostasis, to regulate the smooth muscle contractile state.

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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
          2003
          February 2003
          26 March 2003
          : 40
          : 1
          : 1-10
          Affiliations
          aSmooth Muscle Physiology Group, Cardiovascular Research, University of Manchester, Manchester Royal Infirmary, bMaternal and Fetal Health Research Centre, Human Development and Reproductive Health Research, University of Manchester, St. Mary’s Hospital, Manchester, UK
          Article
          68940 J Vasc Res 2003;40:1–10
          10.1159/000068940
          12644721
          © 2003 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
          Figures: 6, References: 33, Pages: 10
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