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      Induction of Nitric Oxide and Tetrahydrobiopterin Synthesis by Lipoteichoic Acid from Staphylococcus aureus in VascularSmooth Muscle Cells

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          Abstract

          Lipoteichoic acid (LTA), a component of the membrane of gram-positive bacteria, induces an isoform of nitric oxide (NO) synthase (iNOS) in vascular smooth muscle; this process may be associated with the vascular failure observed in gram-positive septic shock. The aim of the present work was to study the cellular mechanisms involved in the induction of NO synthesis by LTA from Staphylococcus aureus in cultured rat vascular smooth muscle cells. LTA induces the gene expression of iNOS and GTP cyclohydrolase I (GTPCH) as well as the formation of NO and tetrahydrobiopterin (BH4), effects which are synergistic with interferon-γ. 2,4-Diamino-6-hydroxypyrimidine (DAHP), a selective inhibitor of GTPCH, inhibits both the increase in cellular levels of BH4 as well as the concomitant formation of NO caused by LTA in combination with interferon-γ. This inhibition by DAHP is reversed by co-addition of sepiapterin which is a substrate for BH4 synthesis. Thus, BH4 synthesis is an absolute requirement for the induction of NO synthesis by LTA in vascular smooth muscle. Our findings also suggest that interrupting pterin synthesis may be an effective target for pharmacologic interventions aimed at limiting NO overproduction in gram-positive shock.

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          Most cited references 2

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          Cloning of Inducible Nitric Oxide Synthase in Rat Vascular Smooth Muscle Cells

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            GTP Cyclohydrolase I mRNA Is Induced by LPS in Vascular Smooth Muscle: Characterization, Sequence and Relationship to Nitric Oxide Synthase

             Y Hattori,  S.S. Gross (1993)
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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
              1998
              April 1998
              16 April 1998
              : 35
              : 2
              : 104-108
              Affiliations
              a Department of Endocrinology, Dokkyo University School of Medicine, Mibu, b Department of Biochemistry, Meikai University School of Dentistry, Sakado, Japan; c Department of Pharmacology, Cornell University Medical College, New York, N.Y., USA; d The William Harvey Research Institute, St. Bartholomew’s Hospital Medical College, London, UK
              Article
              25571 J Vasc Res 1998;35:104–108
              10.1159/000025571
              9588873
              © 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: 22, Pages: 5
              Categories
              Research Paper

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