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Mechanisms of Abnormal Endothelium-Dependent Vascular Relaxation in Atherosclerosis: Implications for Altered Autocrine and Paracrine Functions of EDRF
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Abstract
The present studies were performed to determine if abnormal endothelium-dependent vascular relaxation in atherosclerosis is due to decreased production or release of endothelium-derived relaxing factor (EDRF) by atherosclerotic rabbit vessels or if atherosclerotic vessels are less sensitive to the relaxing effects of EDRF. EDRF release was quantified using two approaches, by the response of bioassay detector vessels and also by the activation of guanylate cyclase within cultured endothelial cells. Using these assays, atherosclerotic vessels were found to release significantly less EDRF than normal vessels in response to both receptor- and nonreceptor-mediated stimuli. Relaxations of normal and atherosclerotic vessels to luminally applied EDRF (derived from normal rabbit aortas stimulated by the calcium ionophore, A23187) and nitric oxide, a putative EDRF, were also studied. Atherosclerotic vessels were more sensitive to EDRF than normal vessels, and equally sensitive to nitric oxide. Additional studies performed in organ chambers failed to demonstrate augmented constriction of atherosclerotic vessels in response to acetylcholine in the presence or absence of methylene blue or LY83583, compounds which inhibit the effect of EDRF. We conclude that decreased EDRF release is the principal underlying mechanism responsible for abnormal endothelium-dependent vascular relaxation in atherosclerosis.
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158779 Blood Vessels 1989;26:300–314Copyright: 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.