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      Gene Expression of Endothelin-1 and ET A and ET B Receptors in Human Cirrhosis: Relationship with Hepatic Hemodynamics

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          Abstract

          Previous experimental studies have suggested that the paracrine endothelin system may participate in the regulation of hepatic hemodynamics in cirrhosis. The present study assesses the relationship between increased portal pressure and preproET-1, ET<sub>A</sub> receptor and ET<sub>B</sub> receptor gene expression in human cirrhosis. PreproET-1, ET<sub>A</sub> receptor and ET<sub>B</sub> receptor mRNA abundance was estimated by quantitative PCR in human hepatic tissue from subjects with normal liver and in cirrhotic patients in whom a hepatic hemodynamic study was performed. The expression of the three transcripts was significantly higher in liver samples of cirrhotic patients than in those obtained from subjects without any histological alteration. Moreover, while no significant correlation was found between preproET-1 mRNA abundance and portal pressure, there was a highly significant direct relationship between ET<sub>A</sub> and ET<sub>B</sub> receptor gene expression and portal pressure in cirrhotic patients. These results indicate that the liver paracrine endothelin system is overactivated in human cirrhosis and that a direct relationship exists between endothelin receptor mRNA abundance and the degree of portal hypertension in these patients.

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          Most cited references 5

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          Molecular characterization of endothelin receptors

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            Characterization of endothelin receptors mediating rat hepatic stellate cell contraction.

             D Rockey (1995)
            Hepatic stellate cells (Ito cells) are perisinusoidal cells with features typical of tissue pericytes which have been implicated in the modulation of sinusoidal blood flow. They possess endothelin (ET) receptors and contract in response to ETs. To elucidate the role of ET receptors in stellate cell contraction, a model cell contraction system was used to examine the effect of ET-1, ET-3, sarafotoxin S6C (a pure ETB receptor agonist) and ETA and/or ETB receptor antagonists. ET-1 and sarafotoxin S6C elicited similar contractile responses (EC50 0.18 and 0.21 nM, respectively). BQ-123, an ETA antagonist, minimally inhibited ET-1 induced contraction, while bosentan, a mixed, nonpeptide ETA/ETB antagonist, inhibited ET-1 and sarafotoxin S6C mediated contraction in a similar fashion. In contrast, bosentan had little effect on ET-3 stimulated contraction. The data demonstrate that the ETB receptor is a prominent mediator of stellate cell contraction and raise the possibility of a novel ET receptor subtype.
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              Influence of the H-subunit and Fe2+on electron transport from I−to QAin Fe2+-free and/or H-free reaction centers fromRhodobacter sphaeroidesR-26

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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
                June 1998
                09 June 1998
                : 35
                : 3
                : 186-193
                Affiliations
                a Hormonal Laboratory and b Liver Unit, Hospital Clínic i Provincial, University of Barcelona, Spain
                Article
                25583 J Vasc Res 1998;35:186–193
                10.1159/000025583
                9647333
                © 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: 4, Tables: 1, References: 29, Pages: 8
                Categories
                Research Paper

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