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      Regional Production of Nitric Oxide after a Peripheral or Central Low Dose of LPS in Mice

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          Abstract

          Nitric oxide (NO) plays a key role in the pathophysiology of inflammation and sepsis. The regulation of the peripheral inducible NO synthase (iNOS – responsible for the massive NO synthesis in inflammation) has been extensively studied in sepsis, but little is known about the actual NO production and its dependence on the location of the primary stimulus (endotoxin, LPS). We measured the activation of the NO pathway after a central (intracerebro-ventricular) or systemic (intravenous) low dose of LPS (2.5 µg/mouse) in three ways: the accumulation of its stable end products (nitrites/nitrates) in the circulation, the induction of iNOS mRNA and the decrease in sodium nitroprus-side-dependent ADP ribosylation of proteins in the liver and brain. Plasma nitrites/nitrates increased after LPS by either route. iNOS mRNA was induced in the liver after intravenous and, to a lower extent, in the brain after intracerebroventricular LPS. Ex vivo ADP ribosylation was decreased in both organs after both administration routes, although to different degrees (higher in the liver after intravenous and in the brain after intracerebroventricular administration), suggesting that NO had been produced in the periphery and in the brain after both routes of LPS administration, despite the fact that no LPS is expected to reach the brain after peripheral low-dose injection. Our data thus demonstrate a cross-talk between periphery and brain in the regulation of NO by LPS. Additionally, the possibility of iNOS-independent NO synthesis stimulated by LPS is implied by the discrepancy between the amount of local NO production suggested by ADP ribosylation and the iNOS mRNA levels.

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          Author and article information

          Journal
          NIM
          Neuroimmunomodulation
          10.1159/issn.1021-7401
          Neuroimmunomodulation
          S. Karger AG
          1021-7401
          1423-0216
          1996
          1996
          23 July 1997
          : 3
          : 6
          : 364-370
          Affiliations
          a Istituto di Ricerche Farmacologiche ‘M. Negri’, b 1° Dipartimento di Ostetricia e Ginecologia, Università di Milano, Milano, Italy
          Article
          97297 Neuroimmunomodulation 1996;3:364–370
          10.1159/000097297
          9266548
          © 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: 7
          Categories
          Original Paper

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