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      Endogenous Inhibitors of Nitric Oxide Synthesis:How Important Are They?

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      Cardiorenal Medicine

      S. Karger AG

      Nitric oxide, Methylarginines, <italic>L</italic>-Arginine

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          Abstract

          In animals and humans, inhibition of nitric oxide (NO) production has widespread effects. Reduced activity of the NO:cyclic GMP pathway has been documented in disease states, including hypertension, diabetes and certain types of renal disease. Inhibitors of NO synthesis occur endogenously, and have been implicated in the regulation of the NO pathway in health and disease. Here we review the possible biological roles of endogenous NO synthase inhibitors, with particular reference to renal disease.

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          Hypertension in mice lacking the gene for endothelial nitric oxide synthase.

          Nitric oxide (NO), a potent vasodilator produced by endothelial cells, is thought to be the endothelium-dependent relaxing factor (EDRF) which mediates vascular relaxation in response to acetylcholine, bradykinin and substance P in many vascular beds. NO has been implicated in the regulation of blood pressure and regional blood flow, and also affects vascular smooth-muscle proliferation and inhibits platelet aggregation and leukocyte adhesion. Abnormalities in endothelial production of NO occur in atherosclerosis, diabetes and hypertension. Pharmacological blockade of NO production with arginine analogues such as L-nitroarginine (L-NA) or L-N-arginine methyl ester affects multiple isoforms of nitric oxide synthase (NOS), and so cannot distinguish their physiological roles. To study the role of endothelial NOS (eNOS) in vascular function, we disrupted the gene encoding eNOS in mice. Endothelium-derived relaxing factor activity, as assayed by acetylcholine-induced relaxation, is absent, and the eNOS mutant mice are hypertensive. Thus eNOS mediates basal vasodilation. Responses to NOS blockade in the mutant mice suggest that non-endothelial isoforms of NOS may be involved in maintaining blood pressure.
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            Author and article information

            Journal
            EXN
            Nephron Exp Nephrol
            10.1159/issn.1660-2129
            Cardiorenal Medicine
            S. Karger AG
            1660-2129
            1998
            June 1998
            22 May 1998
            : 6
            : 3
            : 195-199
            Affiliations
            Centre for Clinical Pharmacology and Therapeutics, Cruciform Project, and Department of Medicine, University College, London, UK
            Article
            20523 Exp Nephrol 1998;6:195–199
            10.1159/000020523
            © 1998 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
            Figures: 3, References: 19, Pages: 5
            Product
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/20523
            Categories
            Minireview

            Cardiovascular Medicine, Nephrology

            Nitric oxide, Methylarginines, <italic>L</italic>-Arginine

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