Background: Chronic activation of β-adrenoceptors (β-ARs) results in cardiac myocyte injury, even death, and diminishes the number of β-ARs. Objectives: To investigate the effects of overexpression of β1- or β2-AR on cardiomyocytes injured by isoprenaline (ISO). Methods: We have used an adenoviral vector carrying the sequence for human β1- or β2-AR (Adv.β1, Adv.β2) to increase the content of β1 or β2-AR in isolated adult rat ventricular myocytes, and we have examined the cell survival and the expression of Bax and Bcl-2. Results: With use of adenoviral vectors, the β1- and β2-AR contents of myocytes were increased 2.98- and 2.87-fold, respectively. Overexpression of β1-AR sharpened the cellular injury of ISO. If β2-AR activity was further blocked by addition of selective β2-AR antagonist ICI118,551, the cells were more sensitive to the impairment of Adv.β1 + ISO. Overexpression of Adv.β2 partially inversed the cytotoxicity of ISO stimulation. The beneficial effects were strengthened by addition of CGP20712A, a β1-AR-blocking agent. Western blot analysis demonstrated that both increasing β1-AR and inhibition of β2-AR increased the ratio of Bax/Bcl-2. Whereas, increasing β2-AR and inhibition of β1-AR decreased the ratio of Bax/ Bcl-2. Control adenovirus CGP had no effect on cell survival. Conclusions: Overexpression of Adv.β2 and/or inhibition of β1-AR have protective effect on adult rat ventricular myocytes chronically stimulated by ISO. Overexpression of Adv.β1 and/or inhibition of β2-AR are deleterious in the same state. The effects of β-ARs on cell survival might be mediated by the Bax/Bcl-2 signal pathway.

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.