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      Dose-Related Changes in the Mechanical Properties of the Carotid Artery in WKY Rats and SHR following Relaxation of Arterial Smooth Muscle

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          Abstract

          Acute converting enzyme inhibition relaxes arterial smooth muscle and increases arterial complicance in several models of animal and human hypertension. However, it is unknown whether the doses needed for the relaxation of large arteries are similar to those inducing arteriolar relaxation and blood pressure (BP) decrease. To answer this question, we used a previously described model of the in situ carotid artery to determine the pressure-volume relationship over a range of transmural pressures from 25 to 200 mm Hg in normotensive rats (WKY) and spontaneously hypertensive rats (SHR). The pressure-volume relation was determined after an acute single oral administration of either a placebo or the converting enzyme inhibitor quinapril given at two different doses (0.3 or 3 mg/kg). At the end of each experiment, the total relaxation of arterial smooth muscle was achieved after a local administration of potassium cyanide (KCN). In the WKY placebo group, from 25 to 100-125 mm Hg transmural pressure, carotid compliance increased and reached a maximum value at 100-125 mm Hg (i.e. close to the operating range of systemic mean BP of the animals), and decreased thereafter. In the SHR placebo group, carotid compliance was significantly lower than in the WKY placebo group for transmural pressure up to 125 mm Hg, and thereafter was equal or even higher; the maximum value of compliance was reached at 125-150 mm Hg transmural pressure, i.e. substantially less than the operating range of the systemic mean BP of the SHR placebo (180 mm Hg). For transmural pressure steps up to 100 mm Hg in WKY and 125 mm Hg in SHR, both doses of quinapril produced an identical relaxation of arterial smooth muscle which approximated 80-90% of the maximum relaxation produced by KCN. For higher transmural pressure levels, neither quinapril nor KCN were able to change compliance values. Although the two doses caused the same degree of arterial smooth muscle relaxation in SHR, operating carotid compliance was substantially increased only with the higher dose, i.e. the dose which significantly shifted the operating systemic BP towards normotensive levels. The study provides evidence that, although low, nonhypertensive doses of quinapril are able to induce maximal relaxation of the carotid artery, operating compliance is substantially increased only if blood pressure is significantly decreased.

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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
          1993
          1993
          23 September 2008
          : 30
          : 1
          : 23-29
          Affiliations
          aDepartment of Internal Medicine, Hypertension Research Center and INSERM U-337 and Broussais Hospital, bINSERM U141, Lariboisière Hospital, Paris, France
          Article
          158971 J Vasc Res 1993;30:23–29
          10.1159/000158971
          8435469
          © 1993 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: 7
          Categories
          Research Paper

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