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      Role of Endothelial Nitric Oxide in the Response to Angiotensin II of Small Mesenteric Arteries of the Rat

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          Abstract

          The role of endothelium-derived nitric oxide (NO) in the vascular contractile response to angiotensin II (Ang II) has been investigated in isolated small mesenteric resistance arteries of the rat. Both contraction and intracellular Ca<sup>2+</sup> ion concentration ([Ca<sup>2+</sup>]<sub>i</sub>) were monitored in vessels, with and without functional endothelium, which were exposed to physiological salt solution containing 25 mM KC1. Ang II induced concentration-dependent contractile responses and increases in [Ca<sup>2+</sup>]<sub>i</sub> which, at the concentration giving the maximal response (10 nM), were not sustained in arteries with functional endothelium; however, the presence of a functional endothelium did not modify the peak responses. Ang II did not increase the cyclic guanosine 3’,5’-monophos-phate content of the tissue nor did it induce relaxation in arteries precontracted with 3 µM noradrenaline. The decline of the Ang II responses was suppressed by removal of the endothelium or by exposure of arteries with endothelium to either the NO synthase inhibitor, N<sup>ω</sup>-nitro- L-arginine methyl ester (300 µM), or the cyclic GMP-dependent protein kinase inhibitor, Rp-8-bro moguanosine 3’, 5’-cyclic monophosphorothioate (30 µM). On the other hand, the NO donor SIN-1 (3-morpholino-sydnonimine, 10 µM) accelerated the decline in [Ca<sup>2+</sup>]<sub>i</sub> and contraction. These results show that endothelium-derived NO does not affect the magnitude of the phasic element of the response to Ang II, but is involved in the rapid attenuation of the tonic component. Activation of cyclic GMP-dependent protein kinase accounts for this effect of endothelium-derived NO.

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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
          1996
          1996
          24 September 2008
          : 33
          : 5
          : 386-394
          Affiliations
          Laboratoire de Pharmacologie et Physiopathologie Cellulaires, Université Louis-Pasteur de Strasbourg, Illkirch, France
          Article
          159167 J Vasc Res 1996;33:386–394
          10.1159/000159167
          8862144
          © 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.

          Page count
          Pages: 9
          Categories
          Research Paper

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