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      Antiatherogenic Action of Nitrendipine in Hypercholesterolemic Rabbits: Changes in Aortic Macrophage Accumulation and Smooth Muscle Cell Phenotype

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          Abstract

          Intimal accumulation of macrophages and changes in the phenotype and growth properties of vascular smooth muscle cells (SMCs) represent key events in the development of atherosclerotic lesions. Here we report on the in vivo effect exerted by nitrendipine on aortic tissue of cholesterol-fed rabbits. We have focused especially on the myosin heavy chain (MyHC) pattern expressed by aortic SMC, taken as a marker of cell differentiation. Using monoclonal antibodies specific to the different forms of MyHC, three differentiation steps were determined: adult, postnatal, and fetal. Nitrendipine administered in conjunction with a cholesterol-enriched diet reduced the development of atherosclerotic lesions (atherosclerosis index: 0.21 vs. 0.32 in untreated animals, p < 0.005), despite persistently high serum cholesterol levels. Compared to untreated controls, nitrendipine-treated animals displayed a decreased number of postnatal-type SMCs in the media underlying the plaque (prevalence index: 0.07 vs. 0.26, p < 0.0001 and a lower aortic cholesterol content (free cholesterol: 3.3 vs. 11.5 ng/mgp < 0.0001; esterified cholesterol: 7.2 vs. 40.5 ng/mg, p < 0.0001). Moreover, nitrendipine treatment decreased the intimal accumulation of macrophages and fetal-type SMCs. It is conceivable that calcium antagonists may exert their antiatherogenic effect, at least in part, through cellular changes unrelated to the classical risk factors.

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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
          1996
          1996
          24 September 2008
          : 33
          : 1
          : 5-12
          Affiliations
          aInstitute of Clinical Medicine, and bDepartment of Biomedical Sciences, University of Padova, and cDepartment of Pharmacology, Bayer S.p.A., Milan, Italy
          Article
          159126 J Vasc Res 1996;33:5–12
          10.1159/000159126
          8603127
          © 1996 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: 8
          Categories
          Research Paper

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