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      Stroke-Prone SHR Vascular Muscle Ca 2+ Current Amplitudes Correlate with Lethal Increases in Blood Pressure

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          Abstract

          Studies on the possible causal relationship between the Ca<sup>2+</sup> channel current density in the vascular muscle cell (VMC) and increases in blood pressure were extended by a comparison of stroke-prone spontaneously hypertensive rats (SP-SHR) with N/nih outbred normotensive rats. Maximal amplitudes of both L-type and T-type Ca<sup>2+</sup> channel currents were significantly increased in SP-SHR without a difference in cell capacitance. SP-SHR peak current amplitudes in 20 mM Ba<sup>2+</sup> averaged 446 ± 64 pA while N/nih averaged 156 ± 25 pA (clearly separated statistically). Both L-type and T-type Ba<sup>2+</sup> currents (I<sub>Ba</sub>) were significantly increased in SP-SHR, shown also by peak current frequency distributions. There was a significant shift to the left of both activation (7 mV) and inactivation (15 mV) current-voltage (I-V) plots. SP-SHR I<sub>Ba</sub> recovery from inactivation was significantly slower (103 versus 61 ms) than in N/nih VMC. The increases in SP-SHR I<sub>Ba</sub> amplitude under maximized conditions correlated with increases in blood pressure. Together with earlier observations of increased vascular muscle Ca<sup>2+</sup> current density coexistent with blood pressure elevation in Kyoto-Wistar SHR, these data provide evidence for altered function of Ca<sup>2+</sup> channels as a fundamental component of hypertension. Since the Ca<sup>2+</sup> channel alterations exist in venous VMCs of newborn SP-SHR rats (in a low pressure blood vessel and at a time when increased Ca<sup>2+</sup> current density could not be an effect of increased blood pressure), our results add to the growing evidence of Ca<sup>2+</sup> channel abnormalities as a cause of genetic hypertension.

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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
          1994
          1994
          23 September 2008
          : 31
          : 6
          : 359-366
          Affiliations
          Oregon Regional Primate Research Center and Departments of Medicine and Cell Biology and Anatomy, Oregon Health Sciences University, Beaverton, Oreg., USA
          Article
          159064 J Vasc Res 1994;31:359–366
          10.1159/000159064
          7986960
          © 1994 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: 8
          Categories
          Research Paper

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