Accumulating evidence suggests that the adrenergic receptors (ARs) play an important role in cardiac diseases. The expression of β3-AR has been recently demonstrated in atria, however, its role in atrial structural remodeling of atrial fibrillation (AF) is unclear. Therefore, the present study was designed to investigate the role of β3-AR in atrial structural remodeling in AF and to clarify its possible mechanisms. Twenty-eight dogs were randomly divided into sham, pacing, β3-AR agonist (BRL37344) and β3-AR antagonist (L748337) groups. AF was induced by rapid atrial pacing at 600 beats per minute for 3 weeks and evaluated by determining the ultrastructure and function of atria. The expression of β3-AR and p38 mitogen-activated protein kinase (MAPK) was examined by western blot, immunohistochemistry and real-time RT-PCR. Additionally, the extent of oxidative stress was tested. We found the atrial enlargement and dysfunction in pacing group. Moreover, atrial interstitial fibrosis, apoptosis and oxidative stress were increased and the levels of β3-AR and phosphorylated p38 MAPK were increased after pacing. Activation of β3-AR exacerbated the pathologic changes and oxidative stress, which were effectively inhibited by L748337. We concluded that β3-AR was upregulated in paced atria, which contributed to oxidative stress and exacerbated atrial structural remodeling by regulating p38 MAPK. Our study provides novel insights into the pharmacological role of β3-AR in AF.

This content is only available via PDF.
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.