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      Effect of Nicorandil, N-(2-Hydroxyethyl)nicotinamide Nitrate, a New Anti-Anginal Agent, on Contractile Responses to Alpha-1- and Alpha-2-Adrenoceptor Agonists in Isolated Rabbit Aorta

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          Abstract

          Effects of nicorandil on contractile responses to α<sub>1</sub>- and α<sub>2</sub>adrenoceptor agonists were examined in isolated rabbit aorta. Nicorandil (10<sup>–6</sup> or 10<sup>–5</sup> M) inhibited contractile responses to clonidine (CL) and BHT-920 in a concentration-dependent manner, but had no effect on the response to methoxamine (MO). Nifedipine (10<sup>–6</sup> and 10<sup>–5</sup> M) had no significant effect on responses to CL and MO, but it had a noticeable inhibitory effect on the response to BHT-920. In tissues pretreated with phenoxybenzamine, nicorandil (10<sup>–5</sup> M) inhibited the residual response to MO, and nifedipine (10<sup>–5</sup> M) inhibited responses to MO and CL. The relationship between maximum contraction and percent receptor occupancy was found to be nonlinear for MO, but was near linear for CL and BHT-920. The inhibitory effect of prazosin (pA<sub>2</sub> of about 9) on MO and CL was much greater than that of yohimbine (pA<sub>2</sub> of about 6). Nicorandil had no apparent or slight inhibitory effect on responses to potassium and Ca<sup>2+</sup>, and this inhibitory effect was much less than that of nifedipine. These results indicate that the responses induced by MO, CL, and BHT-920 in the rabbit aorta are due to activation of α<sub>1</sub>-adrenoceptors. It is also suggested that nicorandil minimally affects voltage-dependent Ca<sup>2+</sup> influx and that differential effects of nicorandil on the responses to α<sub>1</sub> and α<sub>2</sub> agonists may be the result of differeneces in the amount of receptor reserve that exist for MO, CL, and BHT-920 in this blood vessel.

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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
          1986
          1986
          23 September 2008
          : 23
          : 4-5
          : 246-256
          Affiliations
          Department of Pharmacology, School of Medicine, University of Hawaii, Honolulu, Hawaii, and Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A & M University, College Station, Tex., USA
          Article
          158645 Blood Vessels 1986;23:246–256
          10.1159/000158645
          © 1986 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
          Pages: 11
          Categories
          Research Paper

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