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      Involvement of L-Type Calcium Channels in Hypoxic Relaxation of Vascular Smooth Muscle

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          Abstract

          In the systemic vasculature, hypoxia elicits a local vasodilator response that may be partially mediated by ionic channels on vascular smooth muscle, such as adenosine triphosphate sensitive K<sup>+</sup> channels. Recent electrophysiological studies suggest that hypoxia may also inhibit voltage-dependent Ca<sup>2+</sup> channels (L type) on peripheral vascular smooth muscle cells. We hypothesized that hypoxia elicits relaxation of vascular smooth muscle by inhibiting L-type Ca<sup>2+</sup> channels. In endothelium-denuded rat thoracic aortic rings contracted with phenylephrine, mild and moderate hypoxia (PO<sub>2</sub> 35 and 20 mm Hg, respectively) elicited significant relaxation. Pretreatment with the L-type Ca<sup>2+</sup> channel antagonist nifedipine completely inhibited mild hypoxic relaxation and diminished relaxation under moderate hypoxia, whereas glibenclamide, a blocker of adenosine triphosphate sensitive potassium channels, only attenuated the response to moderate hypoxia. In rings contracted with the L-type Ca<sup>2+</sup> channel agonist (–)BAY K 8644 both mild and moderate hypoxia elicited almost complete relaxation. Furthermore, in rings contracted with hyperkalemic solutions (85 m M K<sup>+</sup> or 120 m M K), mild and moderate hypoxia elicited significant relaxations. Thus, we conclude that hypoxia acts directly on vascular smooth muscle to cause relaxation in part by inhibiting L-type Ca<sup>2+</sup> channels.

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          Vasoconstrictor and vasodilator effects of hypoxia.

          Hypoxia has marked effects on artery calibre, which reflects important physiological control mechanisms that are altered in disease states. Hypoxia modifies the release of mediators, especially from the endothelium, and influences smooth muscle membrane potential and Ca2+ regulation. In this review, Roger Wadsworth evaluates the vasoconstrictor and vasodilator effects of hypoxia studied in vitro. In the future, drugs developed to act on the mediators or smooth muscle may be beneficial in the therapy of, for example, pulmonary hypertension or coronary vasospasm.
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            Pharmacological characteristics of receptor-operated and potential-operated Ca2+ channels in rat aorta

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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
              1998
              August 1998
              07 August 1998
              : 35
              : 4
              : 265-273
              Affiliations
              Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, N. Mex., USA
              Article
              25593 J Vasc Res 1998;35:265–273
              10.1159/000025593
              9701711
              © 1998 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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