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      CS-088, an Angiotensin Type 1 Receptor Antagonist, Ameliorated the Impaired Blood Flow in the Optic Nerve Head of Rabbits

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          Abstract

          The effect of CS-088, an angiotensin type 1 receptor antagonist, on optic nerve head (ONH) circulation was investigated in anesthetized rabbits. ONH blood flow was measured for 3 h using laser Doppler flowmetry. ONH blood flow disturbance was induced by intravenous injection of endothelin-1. Blood flow was decreased by 30%; this decrease was reversed by the injection of CS-088. A single injection of CS-088, however, did not alter the baseline ONH blood flow. It is concluded that CS-088 can have a beneficial effect on disturbed ONH blood flow.

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          Most cited references 11

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          Open-angle glaucoma.

           H Quigley (1993)
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            The vascular concept of glaucoma.

            The regulation of ocular perfusion is different for different parts of the eye. Observations on the retina can, therefore, not be extrapolated to the optic nerve head. Extraocular vessels, especially the short posterior ciliary arteries, might play a major role in regulation of ocular circulation, but additional regulation takes place in the eye itself. Dysregulation might be transient and, thus, not necessarily present and detectable at any one examination. Older patients with arteriosclerotic vessels may behave differently in this regard than do young, healthy animals. Not only the arterial but also the venous side of the circulation may be disturbed. Disk hemorrhages can not only be a sign of damage; they can also provoke ischemia. Besides hypoxia, diseased vessel walls might play a direct role in the pathogenesis of optic nerve head cupping. Finally, a relation between vascular dysregulation and aqueous-humor dynamics is conceivable.
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              Modulation of choroidal autoregulation in the rabbit.

               J Kiel (1999)
              Previous studies show that the choroid can maintain its blood flow despite changes in perfusion pressure, behaviour possibly mediated by an autoregulatory mechanism. However, the choroid's rich autonomic innervation suggests possible neural involvement in the response. To evaluate the potential neural contribution, choroidal blood flow was measured by laser Doppler flowmetry over a wide range of perfusion pressure before and after ganglionic blockade in anaesthetized rabbits. Although an upward shift in the pressure-flow (P-F) curve was anticipated due to loss of adrenergic tone, ganglionic blockade shifted the P-F curve downward, prompting a search for a neural vasodilator to explain the response. Cholinergic blockade with atropine failed to alter the P-F curve suggesting little parasympathetic involvement. By contrast, inhibition of nitric oxide (NO) synthase with nitro-L-arginine methyl ester (L-NAME) caused a dramatic downward shift in the P-F curve, suggesting the nitridergic nerves as the source of vasodilatory tone. However, the downward shift in the P-F curve with L-NAME was greater than seen with ganglionic blockade, indicating that endothelial NO rather than neural dilator tone predominates. Moreover, calcium channel blockade after L-NAME reversed the downward shift in the P-F curve suggesting that choroidal vascular tone is modulated by an interaction between NO and an unknown vasoconstrictor. Neither hexamethonium, losartan or a vasopressin antagonist given after L-NAME reversed the downward shift in the P-F curve, ruling out a neural vasoconstrictor, angiotensin II and vasopressin as the source of constrictor tone. Phentolamine given after L-NAME caused a small but significant reversal of the downward shift in the P-F curve, suggesting a minor adrenergic contribution. By contrast, the non-selective endothelin antagonist, A-182086, given after L-NAME significantly attenuated the choroidal constriction. These results indicate that an unknown neural dilator and locally produced NO and endothelin exert competing influences on the inherent reactivity of the choroidal resistance vessels as they respond to changes in perfusion pressure, and that this local regulation is likely modulated by extrinsic neurohumoral factors that are relatively quiet in the anesthetized rabbit.
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                Author and article information

                Journal
                ORE
                Ophthalmic Res
                10.1159/issn.0030-3747
                Ophthalmic Research
                S. Karger AG
                0030-3747
                1423-0259
                2003
                December 2003
                29 December 2003
                : 35
                : 6
                : 351-354
                Affiliations
                aPharmacology and Molecular Biology Research Laboratories and bResearch Institute, Sankyo Company Limited, Tokyo, Japan
                Article
                74076 Ophthalmic Res 2003;35:351–354
                10.1159/000074076
                14688427
                © 2003 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: 2, References: 28, Pages: 4
                Categories
                Original Paper

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