Pharmacology
Original Paper
Cardiorespiratory Responses to D-Ala-2-Me-Phe-4-Met-(O)-ol-Enkephalin after Administration into the Fourth Cerebral Ventricle of the Rat: Interaction with Cholinergic MechanismsRabkin S.W.University of British Columbia, Vancouver, BC, Canada
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Article / Publication Details
Received: June 28, 1990
Accepted: September 13, 1990
Published online: June 06, 2008
Issue release date: 1991
Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0
ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)
For additional information: https://www.karger.com/PHA
Abstract
The purpose of this study was to investigate the effect of the synthetic Met-enkephalin, D-Ala-2-Me-Phe-4-Met-(O)-ol-enkephalin (FK 33-824), on blood pressure, heart rate, respiratory rate and survival, after its injection into the 4th cerebral ventricle of Wistar rats. The animals were either anesthetized with pentobarbital and breathing spontaneously or unanesthetized. The unanesthetized rats were previously instrumented with cannulas in the 4th cerebral ventrical and a systemic artery. In anesthetized rats, intracerebroventricular administration of FK 33-824 produced a transient increase in blood pressure followed by sustained hypotension, bradycardia and respiratory depression in a dose-dependent manner. Fatalities were observed over a 150-min observation period and were a function of dose. Pretreatment with atropine sulfate (1 mg/kg i.v.) produced an accentuated response with greater hypotension, bradycardia and shorter survival. In another group of anesthetized rats, in which hypoventilation was prevented by mechanical ventilation, blood pressure and heart rate were not as reduced as in spontaneously breathing rats. Hypotension, bradycardia and hypoventilation were less marked in unanesthetized rats, compared to anesthetized rats. Thus, FK 33-824 in the 4th cerebral ventricle of the rat produces marked changes in blood pressure in anesthetized as well as unanesthetized animals, but these changes were less in the unanesthetized or mechanically ventilated animal and greater after atropine, suggesting that these effects are mediated by respiratory depression and are antagonized by the cholinergic nervous system.
© 1991 S. Karger AG, Basel
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Article / Publication Details
Received: June 28, 1990
Accepted: September 13, 1990
Published online: June 06, 2008
Issue release date: 1991
Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0
ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)
For additional information: https://www.karger.com/PHA
Copyright / Drug Dosage / Disclaimer
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.
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