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Impairment of Acetylcholine Relaxations by Malondialdehyde, a Marker of Lipid Peroxidation
Abstract
The effect of malondialdehyde (MDA), a lipid peroxidation marker, on the relaxations evoked by acetylcholine (ACh) was analyzed in tail arteries of Sprague-Dawley rats, which have MDA plasma levels of 0.43 ± 0.10 µ M. MDA (0.5–30 µ M) produced an inhibition of ACh relaxations that persisted after repeated washing periods, and was independent of the incubation time. MDA did not modify the vasodilator responses to either exogenous nitric oxide (NO) or sodium nitroprusside, a NO donor. L-Arginine (the NO synthase substrate) did not prevent the impairment of relaxations to ACh caused by MDA. The association of N<sup>ω</sup>-nitro- L-arginine methyl ester (a NO synthase inhibitor) and MDA produced an additive inhibition of the Ach induced relaxations. Superoxide dismutase (a superoxide anion scavenger) completely reversed the inhibitory effect of MDA. These results suggest: (1) MDA is not only a marker of lipid peroxidation but also an agent that can impair endothelium-dependent relaxations; (2) this impairment does not seem to be due to an interference with guanylate cyclase activation by NO or with NO synthase pathway; (3) the effect of MDA appears to be mediated by superoxide anion, and (4) MDA could propagate lipid peroxidation chain reactions in endothelial membranes, that could alter the function of muscarinic receptors.
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159185 J Vasc Res 1996;33:463–470Copyright: 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.