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      Role of Prostacyclin and Nitric Oxide in Regulation of Basal Microvascular Hydraulic Permeability in Cat Skeletal Muscle

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          Abstract

          The effects of prostacyclin, nitric oxide (NO) and β<sub>2</sub>-receptor stimulation on capillary filtration coefficient (CFC) and vascular tone were analyzed in an autoperfused cat skeletal muscle in vivo preparation, to evaluate if these substances are involved in regulation of basal microvascular hydraulic permeability. CFC was increased from control (100%) to 124% with the prostacyclin-synthase inhibitor tranylcypromine and restored by simultaneous infusion of prostacyclin at 0.1 ng·kg<sup>–1</sup>· min<sup>–1</sup>, with further reduction to 76% at 1 ng· kg<sup>–1</sup>·min<sup>–1</sup>. Prostacyclin at these doses did not influence vascular tone. NO inhibition by L-NAME increased CFC to 116% of control, with a vascular resistance increase of 45%. CFC was restored by simultaneous infusion of the NO precursor L-arginine. L-arginine given alone reduced CFC to 86% of control. Tranylcypromine and L-NAME given together increased CFC to 141% of control and CFC was reduced to 86% by prostacyclin at 1 ng·kg<sup>–1</sup>·min<sup>–1</sup> with no significant further reduction by adding L-arginine. Adrenaline alone, in a vasodilating dose verifying β<sub>2</sub> stimulation, or when followed by simultaneous β-blockade with propranolol, did not influence CFC. We conclude that NO and especially prostacyclin are involved in bi-directional regulation of basal microvascular hydraulic permeability and can account for up to 30–40% increase or decrease from a basal value. Physiological β<sub>2</sub> stimulation has no effect on basal hydraulic permeability. The permeability-reducing effects of prostacyclin and NO are additive. NO, but not prostacyclin, is involved in regulation of basal vascular tone.

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          Most cited references 4

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          Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides.

          Prostaglandin (PG) endoperoxides (PGG2 and PGH2) contract arterial smooth muscle and cause platelet aggregation. Microsomes from pig aorta, pig mesenteric arteries, rabbit aorta and rat stomach fundus enzymically transform PG endoperoxides to an unstable product (PGX) which relaxes arterial strips and prevents platelet aggregation. Microsomes from rat stomach corpus, rat liver, rabbit lungs, rabbit spleen, rabbit brain, rabbit kidney medulla, ram seminal vesicles as well as particulate fractions of rat skin homogenates transform PG endoperoxides to PGE- and PGF- rather than to PGX-like activity. PGX differs from the products of enzymic transformation of prostaglandin endoperoxides so far identified, including PGE2, F2alpha, D2, thromboxane A2 and their metabolites. PGX is less active in contracting rat fundic strip, chick rectum, guinea pig ileum and guinea pig trachea than are PGG2 and PGH2. PGX does not contract the rat colon. PGX is unstable in aqueous solution and its antiaggregating activity disappears within 0.25 min on boiling or within 10 min at 37degrees C. As an inhibitor of human platelet aggregation induced in vitro by arachidonic acid PGX was 30 times more potent than PGE1. The enzymic formation of PGX is inhibited by 15-hydroperoxy arachidonic acid (IC50 = 0.48 mug/ml), by spontaneously oxidised arachidonic acid (IC 50 less than 100 mug/ml) and by tranylcypromine (IC50 = 160 mug/ml). We conclude that a balance between formation by arterial walls of PGX which prevents platelet aggregation and release by blood platelets of prostaglandin endoperoxides which induce aggregation is of the utmost importance for the control of thrombus formation in vessels.
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            Sepsis/septic shock

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              Relationship between microvascular permeability and ultrastructure

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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
                1999
                June 1999
                18 June 1999
                : 36
                : 3
                : 245-252
                Affiliations
                Departments of aPhysiological Sciences and bAnaesthesia and Intensive Care, University and University Hospital of Lund, Sweden
                Article
                25648 J Vasc Res 1999;36:245–252
                10.1159/000025648
                10393511
                © 1999 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
                Figures: 5, References: 39, Pages: 8
                Categories
                Research Paper

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