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      Lack of Endotoxin-lnduced Hyporesponsiveness to U46619 in Isolated Neonatal Porcine Pulmonary but Not Mesenteric Arteries

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          Abstract

          The effects of endotoxin from Escherichia coli on the vasoconstrictor responses to noradrenaline (10 n M–100 µ M) and the thromboxane A<sub>2</sub> analog U46619 (100 p M–1 µ M) were evaluated on isolated pulmonary and mesenteric arteries from neonatal piglets. Incubation for 20 h with endotoxin (1 µg ml<sup>–1</sup>) induced a decrease in the contractile responses to noradrenaline in both arteries (p < 0.05) which was inhibited by N<sup>G</sup>-nitro- L-arginine-methyl ester ( L-NAME, 100 µ M). Endotoxin-treated mesenteric arteries also showed a reduction of the maximal contractions induced by U46619 (p < 0.05) and this effect was inhibited by L-NAME. In contrast, the contractile responses to U46619 were similar in control and endotoxin-treated pulmonary arteries. In endothelium-denuded pulmonary rings, endotoxin was also unable to modify the contractile responses to U46619. In pulmonary rings, the contractions induced by U46619 (100 nM) were much less sensitive to sodium nitroprus-side, 8-bromo-cyclic GMP or dipyridamole than those induced by 10 µ M noradrenaline. In conclusion, endotoxin-treated pulmonary arteries exhibited decreased responses to noradrenaline due to enhanced nitric oxide release but not to the thromboxane A<sub>2</sub> analog U46619. This lack of hyporesponsiveness to U46619 in pulmonary arteries may be attributed to a relative insensitivity to nitric oxide. The absence of pulmonary hyporesponsiveness to U46619 may explain why pulmonary hypertension occurs in septic shock despite Ca<sup>2+</sup>-inde-pendent nitric oxide synthase induction in the lung.

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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
          1996
          1996
          24 September 2008
          : 33
          : 3
          : 249-257
          Affiliations
          aDepartment of Pharmacology, Institute of Pharmacology and Toxicology, School of Medicine, Universidad Complutense, and bDivision of Neonatology, Department of Pediatrics, Hospital Universitario S. Carlos, Madrid, Spain
          Article
          159152 J Vasc Res 1996;33:249–257
          10.1159/000159152
          8924522
          © 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: 9
          Categories
          Research Paper

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