L -Arginine: Rediscovery in Progress

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Abstract

Since the recognition that L-arginine (LA) is the natural metabolic donor of nitric oxide, this amino acid has reached the medical spotlight. LA exerts favorable effects in the prevention and treatment of endothelial damage and the restoration of endothelial function in patients with cardiovascular risk factors (hypercholesterolemia, smoking, hypertension, diabetes and advanced age) or with several chronic cardiovascular disorders (coronary, peripheral and cerebral vascular disease, and mild-to-moderate heart failure). LA administration is likely to represent a potentially novel therapeutic strategy during angioplasty, coronary bypass grafting and cardiac transplantation. More conclusive research findings for the rediscovered role of this well-known substance merit close attention.

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Most cited references 7

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Vascular endothelial cells synthesize nitric oxide from L-arginine.

R M Palmer, D Ashton, S Moncada (1988)

Nitric oxide (NO) released by vascular endothelial cells accounts for the relaxation of strips of vascular tissue and for the inhibition of platelet aggregation and platelet adhesion attributed to endothelium-derived relaxing factor. We now demonstrate that NO can be synthesized from L-arginine by porcine aortic endothelial cells in culture. Nitric oxide was detected by bioassay, chemiluminescence or by mass spectrometry. Release of NO from the endothelial cells induced by bradykinin and the calcium ionophore A23187 was reversibly enhanced by infusions of L-arginine and L-citrulline, but not D-arginine or other close structural analogues. Mass spectrometry studies using 15N-labelled L-arginine indicated that this enhancement was due to the formation of NO from the terminal guanidino nitrogen atom(s) of L-arginine. The strict substrate specificity of this reaction suggests that L-arginine is the precursor for NO synthesis in vascular endothelial cells.

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Correction of endothelial dysfunction in coronary microcirculation of hypercholesterolaemic patients by L-arginine

H Just, H Drexler, A.M Zeiher … (1991)

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A novel nonenzymatic pathway for the generation of nitric oxide by the reaction of hydrogen peroxide and D- or L-arginine.

A Koyama, Bruce Hirayama, S Nagase … (1997)

Nitric oxide (NO) is a biologically active molecule known to be enzymatically synthesized from L-arginine in the presence of NO synthetase (NOS). In this study, we demonstrate a novel non-enzymatic pathway for NO synthesis involving hydrogen peroxide and D- or L-arginine. We employed two measures of NO generation. The first consists in the demonstration of the oxidative metabolites of NO (NO2 + NO3 = NOx) and the second is the confirmatory finding of chemiluminescence derived from NO. The results show that NOx increases in the incubation mixture containing hydrogen peroxide coupled with D-arginine, L-arginine, L-canavanine, and even the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). However, chemiluminescence was detected only from the reactions of hydrogen peroxide and D- or L-arginine and was diminished by the addition of carboxy-2-phenyl-4, 4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (PTIO), a specific scavenger of NO, confirming NO generation in the reaction.

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Author and article information

Journal

Journal ID (publisher-id): CRD

Journal ID (nlm-ta): Cardiology

Journal ID (doi): 10.1159/issn.0008-6312

Title: Cardiology

Publisher: S. Karger AG

ISSN (Print): 0008-6312

ISSN (Electronic): 1421-9751

Publication date Subscription-year: 1998

Publication date (Print): December 1998

Publication date (Electronic): 15 October 2008

Volume: 90

Issue: 3

Pages: 153-159

Affiliations

Cardiac Rehabilitation Institute, Chaim Sheba Medical Center, Tel-Hashomer, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

Article

Publisher ID: 6837 Other ID: Cardiology 1998;90:153–159

DOI: 10.1159/000006837

PubMed ID: 9892762

SO-VID: 4fd7052d-2899-4317-986f-e61f00b9dd40

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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.

History

Date received : 09 June 1998

Date accepted : 24 June 1998

Page count

Figures: 2, References: 94, Pages: 7

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L-Arginine: Rediscovery in Progress

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