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      Endothelium-lndependent Relaxations to Acetylcholine and A23187 in the Human Umbilical Artery

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          Abstract

          The effects of acetylcholine (ACh) and A23187 on ring preparations from the human umbilical artery (HUA) were investigated and compared with the rat aorta (RA). The results from the HUA demonstrate that: (1) At both high (pO<sub>2</sub> > 600 mm Hg) and low O<sub>2</sub> tension pO<sub>2</sub> < 55 mm Hg), ACh and A23187 relaxed precontracted rings in a concentration-dependent and endothelium-independent manner. Changes in pO<sub>2</sub> did not influence the responses of the HUA to either relaxant. (2) Relaxation responses of the HUA to either ACh or A23187 were insensitive to methylene blue (50 µ M) , L-nitro-arginine methyl ester (100 µ M) , indomethacin (10 µ M)and nordihydroguaiaretic acid (50 µ M) . Relaxations initiated by ACh were also atropine-resistant. (3) Meclofenamic acid (3 µ M) suppressed the relaxations to A23187, but not ACh. (4) Regardless of pO<sub>2</sub> superoxide dismutase (100 U/ml) potentiated the relaxant effects of ACh, whereas mannitol (60 mM) enhanced ACh-initiated relaxations at high but not low pO<sub>2</sub>. (5) Ouabain (30 n M), high potassium (HK<sup>+</sup>, 60 mM) and tetraethylammonium (20 m M) inhibited responses to ACh. (6) Na<sup>+</sup>-free physiological saline solution inhibited both relaxations and oscillations initiated by either ACh or A23187. (7) Both nitroglycerin and exogenous nitric oxide (NO) fully, and 8-bromoguanosine 3’,5’-cyclic monophosphate partially, relaxed the HUA, and LY83583 (10 µ M) reversed such relaxations. (8) In the RA, relaxation responses to ACh and A23187 were endothelium-dependent and sensitivity was reduced under high versus low pO<sub>2</sub> conditions. We conclude that in the HUA, unlike in the RA, ACh and A23187 mediate their responses via an endothelium- and NO-independent processes), perhaps involving the release of a muscle-derived relaxing factor. ACh-initiated relaxations are mediated by activation of Na<sup>+</sup>, K<sup>+</sup>-ATPase, and subsequent hyperpolarization via K<sup>+</sup> efflux, whereas A23187-mediated relaxations result from the synthesis of an indomethacin-resistant cyclooxygenase product.

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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
          1994
          1994
          23 September 2008
          : 31
          : 2
          : 92-105
          Affiliations
          Department of Pharmacology and Therapeutics, Faculty of Medicine, The Health Sciences Centre, The University of Calgary, Calgary, Canada
          Article
          159035 J Vasc Res 1994;31:92–105
          10.1159/000159035
          8117864
          © 1994 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: 14
          Categories
          Research Paper

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