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      Sympathetic Innervation of Human Mesenteric Artery and Vein

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          Abstract

          Background: Innervation of blood vessels shows inter-species variability. There are few studies on the innervation of human vessels; thus, healthy mesenteric vessels were studied to identify the expression of immunomarkers and the morphology of sympathetic innervation as the basis for a study of mesenteric vessels in inflammatory bowel disease. Methods and Results: Electron microscopy studies examined the relationships of nerves to smooth muscle cells. In veins, nerves were distributed throughout the medial smooth muscle coat, often in close apposition (50 nm) to smooth muscle cells. In arteries, nerves were located at the adventitial-medial border, few closer than 2,000 nm to smooth muscle cells, often with interposing connective tissue and Schwann cell processes. There was a significantly greater nerve density in veins than in arteries (227 vs. 41 mm<sup>2</sup>; p = 0.03). Immunohistochemical studies revealed the presence of sympathetic and sensory-motor nerves in arteries and veins. Conclusions: It is suggested that in humans with an upright stance, the mesenteric venous system plays a particularly important role in controlling mesenteric capacitance, which is reflected by their dense innervation. It is speculated that transmitters released from perivascular nerves supplying the human mesenteric arteries may play a long-term (trophic) role in addition to short-term signalling roles.

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          Most cited references 16

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          Purinergic signaling and vascular cell proliferation and death.

          Evidence for the role of purinergic signaling (via P1 and P2Y receptors) in the proliferation of vascular smooth muscle and endothelial cells is reviewed. The involvement of the mitogen-activated protein kinase second-messenger cascade in this action is clearly implicated, although details of the precise intracellular pathways involved still remain to be determined. Synergistic actions of purines and pyrimidines with growth factors occur in promoting cell proliferation. Interaction between purinergic signaling for vascular cell proliferation and cell death mediated by P2X7 receptors is discussed. There is evidence of the release of ATP from endothelial cells, platelets, and sympathetic nerves as well as from damaged cells in atherosclerosis, hypertension, restenosis, and ischemia; furthermore, there is evidence that vascular smooth muscle and endothelial cells proliferate in these pathological conditions. Thus, the involvement of ATP and its breakdown product, adenosine, is implicated; it is hoped that with the development of selective P1 (A2) and P2Y receptor agonists and antagonists, new therapeutic strategies will be explored.
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            New insights into the local regulation of blood flow by perivascular nerves and endothelium.

            Blood flow, particularly in the skin, is essential for the success of plastic surgical operations. This review describes recent studies of the perivascular nerves and vascular endothelial cells which regulate blood flow. Perivascular nerves, once considered simply adrenergic or cholinergic, release many types of neurotransmitters, including peptides, purines and nitric oxide. Cotransmission (synthesis, storage and release of more than one transmitter by a single nerve) commonly takes place. Some afferent nerves have an efferent (motor) function and axon reflex control of vascular tone by these "sensory-motor" nerves is more widespread than once thought. Endothelial cells mediate both vasodilatation and vasoconstriction. The endothelial cells can store and release vasoactive substances such as acetylcholine (vasodilator) and endothelin (vasoconstrictor). The origins and functions of such vasoactive substances are discussed. Endothelial vasoactive substances may be of greater significance in the response of blood vessels to local changes while perivascular nerves may be concerned with integration of blood flow in the whole organism. The dual regulation of vascular tone by perivascular nerves and endothelial cells is altered by aging and conditions such as hypertension, as well as by trauma and surgery. Studies of vascular tone in disease and after denervation or mechanical injury suggest possible trophic interactions between perivascular nerves and endothelial cells. Such trophic interactions may be important for growth and development of the two control systems, particularly in the microvasculature where neural-endothelial separation is small.
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              Quantification of neurons in the myenteric plexus: an evaluation of putative pan-neuronal markers.

              Accurate estimates of the total number of neurons located in the wall of the gut are essential for studies of the enteric nervous system (ENS). Though several stains and antibodies are used routinely as pan-neuronal markers, controversies of relative sensitivity and completeness have been difficult to resolve, at least in part because comparisons often must be made across experiments and laboratories. Therefore, we evaluated the efficacy of four putative pan-neuronal markers for the ENS, under comparable conditions. Neurons in the myenteric plexus of wholemounts taken from the small intestines of Fischer 344 rats were stained using Cuprolinic Blue, anti-HuC/D, anti-protein gene product 9.5, or FluoroGold injections followed by permanent labeling with an antibody to the FluoroGold molecule. All four markers had useful features, but both protein gene product 9.5 and FluoroGold were found to be problematic for obtaining reliable counts. As a result, only neurons labeled with either Cuprolinic Blue or anti-HuC/D were compared quantitatively. Based on counts from permanently labeled tissue, Cuprolinic Blue and HuC/D were similarly effective in labeling all neurons. Because the two protocols have different strengths and weaknesses, Cuprolinic Blue and HuC/D provide a complementary set of labels to study the total neuronal population of the ENS.
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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
                2008
                June 2008
                03 March 2008
                : 45
                : 4
                : 323-332
                Affiliations
                aAutonomic Neuroscience Centre, and bDepartment of Surgery, Royal Free and University College Medical School, and cDepartment of Anatomy, University College London, London, UK
                Article
                119095 J Vasc Res 2008;45:323–332
                10.1159/000119095
                18311081
                © 2008 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: 6, Tables: 2, References: 29, Pages: 10
                Categories
                Research Paper

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