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      Immunohistochemical and Molecular Characterization of the Differential Response of the Rat Mesenteric Microvasculature to Angiotensin-II Infusion


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          The present study focuses on the differential response of three branch levels of the mesenteric resistance arterial vasculature of 450-gram Sprague-Dawley rats infused continuously with angiotensin II (A-II) for 4, 7 and 14 days at a rate of 435 ng/kg/min, with an associated period of hypertension. The three branch levels (types I, II and III) were characterized by light microscopy and immunostaining using monoclonal antibodies for proliferating cell nuclear antigen, ED-1 (specific for rat monocytes/macrophages) and α smooth muscle cell (SMC) actin. Cross-sectional areas of the vascular walls were determined morphometrically. In situ hybridizations were performed on paraffin sections using both sense and antisense <sup>35</sup>S-labeled cRNA probes generated from rat SMC osteopontin and elastin cDNAs. In the type-I (penetrating) arteries from A-II-infused animals, there was massive fibrinoid necrosis, a marked fibro-proliferative perivascular response, intense monocyte/macrophage infiltration, striking SMC osteopontin and elastin gene expression; SMC, fibroblast and monocyte/macrophage DNA synthesis; and significant increase in the cross-sectional areas of the vascular walls. In the same animals, DNA synthesis also occurred in the larger mesenteric arteries of types II and III where it is associated with significant enlargement of the walls by SMC hypertrophy but without overt morphologic damage. It is suggested that the monocyte/macrophage infiltration and fibroproliferative response of type-I arteries may be related to A-II-induced osteopontin gene expression. Angiotensin infusion in the rat may represent a reproducible model of microvascular injury that can be utilized to elucidate the cellular and molecular biology of a variety of disease states such as hypertension and diabetes mellitus.

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          Author and article information

          J Vasc Res
          Journal of Vascular Research
          S. Karger AG
          24 September 2008
          : 33
          : 3
          : 195-208
          Departments of Pathology, aWayne State University School of Medicine, Detroit, Mich., and bUniversity of Washington, Seattle, Wash., USA
          159148 J Vasc Res 1996;33:195–208
          © 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.

          : 19 June 1995
          : 15 December 1995
          Page count
          Pages: 14
          Research Paper

          General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
          Polyploidy,Angiotensin II,Mesenteric resistance arteries,In situ hybridization,Gene expression,Osteopontin,Elastin,Vascular smooth muscle,Vascular remodeling,Hypertension


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