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      Alpha-1-Adrenoceptor Stimulation Induces Nitric Oxide Release in Rat Pulmonary Arteries

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          Elevation of intracellular calcium in smooth muscle causes endothelial cell generation of NO in arterioles.

          It is well known that vascular smooth muscle tone can be modulated by signals arising in the endothelium (e.g., endothelium-derived relaxing factor, endothelium-derived hyperpolarizing factor, and prostaglandins). Here we show that during vasoconstriction a signal can originate in smooth muscle cells and act on the endothelium to cause synthesis of endothelium-derived relaxing factor. We studied responses to two vasoconstrictors (phenylephrine and KCl) that act by initiating a rise in smooth muscle cell intracellular Ca2+ concentration ([Ca2+]i) and exert little or no direct effect on the endothelium. Fluo-3 was used as a Ca2+ indicator in either smooth muscle or endothelial cells of arterioles from the hamster cheek pouch. Phenylephrine and KCl caused the expected rise in smooth muscle cell [Ca2+]i that was accompanied by an elevation in endothelial cell [Ca2+]i. The rise in endothelial cell [Ca2+]i was followed by increased synthesis of NO, as evidenced by an enhancement of the vasoconstriction induced by both agents after blockade of NO synthesis. The molecule involved in signal transmission from smooth muscle to endothelium is as yet unknown. However, given that myoendothelial cell junctions are frequent in these vessels, we hypothesize that the rise in smooth muscle cell Ca2+ generates a diffusion gradient that drives Ca2+ through myoendothelial cell junctions and into the endothelial cells, thereby initiating the synthesis of 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
            1999
            February 1999
            01 March 1999
            : 36
            : 1
            : 79-81
            Affiliations
            aLaboratory for Physiology, bDepartment of Anesthesiology, Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, cDepartment of Anesthesiology, Thorax Center ‘Ignatius’, Breda, The Netherlands
            Article
            25628 J Vasc Res 1999;36:79–81
            10.1159/000025628
            10050076
            © 1999 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: 1, Tables: 1, References: 4, Pages: 3
            Categories
            Rapid Communication

            General medicine, Neurology, Cardiovascular Medicine, Internal medicine, Nephrology

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