Modulation of Endothelin-1-Induced Cytosolic Free Calcium Mobilization and Mitogen-Activated Protein Kinase Activation by Erythropoietin in Vascular Smooth Muscle Cells

Abstract

Background: It has been reported that human recombinant erythropoietin (rHuEPO) modulates the sensitivity of the cardiovascular system to vasoconstrictors. We investigated whether rHuEPO has modulative effects on the endothelin-1 (ET-1)-induced elevation of cytosolic free calcium concentration ([Ca²⁺]_i) and mitogen-activated protein (MAP) kinase activation in vascular smooth muscle cells (VSMC). Methods: [Ca²⁺]_i was measured by fura-2/AM, and MAP kinase activation was analyzed by Western blotting. Results: Exposure of VSMC to rHuEPO prior to stimulation with ET-1 enhanced both basal and ET-1-induced elevation of [Ca²⁺]_i in a dose-dependent manner in the presence of extracellular Ca²⁺. The synergistic effect was also retained in the absence of extracellular Ca²⁺ after exposure to rHuEPO. However, the effect was diminished in the presence of extracellular Ca²⁺ combined with the intracellular Ca²⁺ release inhibitor TMB-8, PKC inhibitor, or PKC depletion. Exposure to rHuEPO also had a synergistic effect on the activation of MAP kinase induced by ET-1; however, this effect was diminished in the presence of the Ca²⁺ chelator BAPTA-AM. Conclusion: The results suggest that rHuEPO has synergistic effects on ET-1-induced [Ca²⁺]_i mobilization, particularly on intracellular Ca²⁺ release, and MAP kinase activation in VSMC.

Journal

Journal ID (publisher-id): KBR

Journal ID (nlm-ta): Kidney Blood Press Res

Journal ID (doi): 10.1159/issn.1420-4096

Title: Kidney and Blood Pressure Research

Publisher: S. Karger AG

ISSN (Print): 1420-4096

ISSN (Electronic): 1423-0143

Publication date Subscription-year: 2001

Publication date (Print): 2001

Publication date (Electronic): 29 August 2001

Volume: 24

Issue: 3

Pages: 192-200

Affiliations

Department of Nephrology, Jichi Medical School, Tochigi, Japan

Article

Publisher ID: 54227 Other ID: Kidney Blood Press Res 2001;24:192–200

DOI: 10.1159/000054227

PubMed ID: 11528212

Copyright statement: © 2001 S. Karger AG, Basel

License:

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: 7, References: 32, Pages: 9

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Categories

Subject: Original Paper