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      Diminishment of Contractions Associated with Depolarization-Evoked Activation of Ca 2+ Channels in Diabetic Rat Aorta

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          Abstract

          Alterations in contractile responses of aortic rings mediated by activation of Ca<sup>2+</sup> channels were investigated in rats with streptozotocin-induced diabetes. Eight to 12 weeks of diabetes resulted in a marked decrease in the contractile response of aortic rings to high K<sup>+</sup>. In contrast, diabetic aortas exhibited significantly greater contractions in response to noradrenaline compared to age-matched controls. In the presence of 15 ml K<sup>+</sup>, the Ca<sup>2+</sup> channel agonist Bay K 8644 consistently produced concentration-dependent contractions in control aortas. On the other hand, the half of diabetic aortas did not respond to Bay K 8644. As a result, the contractile response to Bay K 8644 was significantly less in diabetic aortas compared to controls. There was no significant difference in basal <sup>45</sup>Ca<sup>2+</sup> uptake between control and diabetic aortas. However, the uptake of <sup>45</sup>Ca<sup>2+</sup> induced by high K<sup>+</sup> was significantly less in diabetic aortas than in controls, and pretreatment with the Ca<sup>2+</sup> channel antagonist nifedipine abolished both responses. The resting membrane potentials were not significantly different between control and diabetic aortas. Furthermore, no difference was found in the magnitude of depolarization evoked by increasing K<sup>+</sup> concentrations between the two groups of tissues. There were no significant differences in the density and the dissociation constant for [<sup>3</sup>H]-(+)-PN200-110, a radiolabeled Ca<sup>2+</sup> channel antagonist, between aortic membranes from control and diabetic rats. These data indicate that the contractile responses to high K<sup>+</sup> and Bay K 8644 are specifically diminished in diabetic aortas. These diminished responses are not due to a difference in the number of Ca<sup>2+</sup> channels, but may be related to an alteration in activation of the channels by membrane depolarization.

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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
          1996
          1996
          24 September 2008
          : 33
          : 6
          : 454-462
          Affiliations
          Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan
          Article
          159184 J Vasc Res 1996;33:454–462
          10.1159/000159184
          8998194
          © 1996 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: 9
          Categories
          Research Paper

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