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      Heterogeneity of Vascular Smooth Muscle Responsiveness to Lipid Vasoactive Mediators

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          Abstract

          Thromboxane A<sub>2</sub> (TxA<sub>2</sub>), leukotriene C<sub>4</sub> (LTC4), leukotriene D<sub>4</sub> (LTD<sub>4</sub>), and platelet-activating factor (PAF) are novel lipids which exert a variety of biological actions. TxA<sub>2</sub>, LTC<sub>4</sub> and LTD<sub>4</sub> have been shown to induce direct vasoconstriction in several species, while PAF contracts isolated guinea pig ileum and lung parenchyma. We studied the direct vasoconstricting activities of these lipid mediators in isolated cat renal, superior mesenteric and coronary arteries. The TxA<sub>2</sub> analog 9, 11-methanoepoxy PGH<sub>2</sub> (U-46619) constricted both perfused and helical strips, with the renal and mesenteric arteries being 4 times more responsive than the coronary arteries. LTC4 and LTD<sub>4</sub> constricted coronary arteries to a significantly greater extent than renal and superior mesenteric arteries in both perfused arteries and helical strips. Furthermore, PAF failed to contract any of the perfused arteries or helical strips at concentrations from 1 ng to 20 µg. TxA<sub>2</sub> was a potent vasoconstrictor in all the vessels studied, suggesting a role for this substance as a vasoactive mediator in ischemia and shock. The coronary arteries were more responsive to the leukotrienes than the mesenteric and renal arteries, suggesting that the leukotrienes may play an important role in myocardial ischemia. Moreover, both thromboxane and leukotriene effects were blocked in all preparations by specific receptor antagonists. While the biological effects of PAF are still poorly understood, PAF does not directly vasoconstrict large arteries of the feline renal, superior mesenteric or coronary vasculatures.

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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
          1987
          1987
          23 September 2008
          : 24
          : 1-2
          : 24-30
          Affiliations
          Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa., USA
          Article
          158668 Blood Vessels 1987;24:24–30
          10.1159/000158668
          © 1987 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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