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      Role of T Channels in Cardiovascular Function

      Cardiology

      S. Karger AG

      L- versus T-channel selectivity, T-channel calcium blocker, Mibefradil, Cardiovascular function

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          Abstract

          Although two types of Ca<sup>2+</sup> channels are found to occur in the cardiovascular system, very little is known about one of them, primarily because a pharmacological blocking agent has been lacking. The enigmatic transient (T)-type Ca<sup>2+</sup> channel has finally been recognized by a selective Ca<sup>2+</sup> antagonist. The novel tetralol Ca<sup>2+</sup> antagonist, mibefradil, is a selective T-type Ca<sup>2+</sup> channel blocker that produces effective vasodilatation with additional inhibitory actions on blood vessel wall and left ventricular thickening. The availability of a blocking agent has begun to reveal the significance of T-type Ca<sup>2+</sup> channel signals. Selective T-type Ca<sup>2+</sup> channel blockade characteristics include vascular selectivity, freedom from negative cardiac inotropism, consistent and predictable reduction in heart rate, reduction in subendothelial proliferation, and increased survival of severely hypertensive and heart failure animal models. Mibefradil increases coronary blood flow without increasing myocardial oxygen consumption, and by decreasing heart rate and thus time spent in diastole, improves subendocardial perfusion. Improved perfusion of the myocardial wall and lowered heart rate appear to normalize the underlying pathophysiological factors, improve heart failure, and provide long-term protection. Thus, T-type Ca<sup>2+</sup> channel blockade offers significant new cardiovascular protective benefits, even in the presence of critical pathophysiological elements (i.e. increased heart rate and neurohumors in the presence of decreased ejection fraction and contractility) found in heart failure.

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          Mibefradil, a Selective Calcium T-Channel Blocker, in Stroke-Prone Spontaneously Hypertensive Rats

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            Mechanism of the Antiischemic Effect of Mibefradil, a Selective T Calcium Channel Blocker in Dogs: Comparison with Amlodipine

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              Effect of Mibefradil on Left Ventricular Diastolic Function in Patients with Congestive Heart Failure

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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                978-3-8055-6662-9
                978-3-318-00285-0
                0008-6312
                1421-9751
                1998
                February 1998
                03 March 1998
                : 89
                : Suppl 1
                : 2-9
                Affiliations
                Oregon Regional Primate Research Center, and Departments of Medicine and Cell and Developmental Biology, Oregon Health Sciences University, Beaverton, Oreg., USA
                Article
                47273 Cardiology 1998;89(suppl 1):2–9
                10.1159/000047273
                9570423
                © 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: 3, Tables: 1, References: 46, Pages: 8
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