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      Effects of Renal Arterial Endothelin-1 and Endogenous Endothelins on Regional Kidney Blood Flow and Renal Antihypertensive Mechanisms in Anesthetized Rabbits

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          Abstract

          To determine how endothelins affect regional kidney blood flow and responses to increased renal artery pressure (RAP), an extracorporeal circuit was established to control RAP independent of the mean systemic arterial pressure (MAP). RAP was first set at ∼65 mm Hg, and endothelin-1 (1 ng/kg/min for 30 min then 0.4 ng/kg/min) or vehicle was infused into the renal artery, or the ET<sub>A</sub>/ET<sub>B</sub> antagonist TAK-044 (3 mg/kg plus 3 mg/kg/h) or vehicle was administered intravenously. RAP was then progressively increased in steps from ∼65 to ∼160 mm Hg. When RAP was ∼65 mm Hg, endothelin-1 increased renal vascular resistance (RVR, 72%), and reduced cortical (CBF, 26%) but not medullary blood flow (MBF). TAK-044 reduced MAP (12%) and RVR (15%) and increased CBF (21%) but not MBF. When RAP was increased, renal blood flow (RBF), glomerular filtration rate, and urine and sodium excretion increased, while MAP fell. These responses were unaffected by endothelin-1. TAK-044 potentiated the increases in RBF and reductions in MAP in response to increased RAP, but did not affect urine and sodium excretion. Plasma renin activity was reduced by endothelin-1 and increased by TAK-044. Thus, both exogenous and endogenous endothelins reduce CBF but not MBF, and reduce plasma renin activity, but neither affect pressure natriuresis.

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          Effects of endothelin on renal regional blood flow in dogs

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            Renal haemodynamic effects of endothelin-1 and the ETA/ETB antagonist TAK-044 in anaesthetized rabbits

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              Effect of endothelin blockade on pressure natriuresis in nitric oxide-deficient hypertensive rats

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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2000
                2000
                02 November 2000
                : 23
                : 6
                : 366-375
                Affiliations
                aDepartment of Physiology, Monash University, Clayton, Vic., Australia, and bDepartment of Physiology, Institute of Physiology and Pharmacology, University of Göteborg, Sweden
                Article
                25985 Kidney Blood Press Res 2000;23:366–375
                10.1159/000025985
                11070416
                © 2000 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: 1, References: 34, Pages: 10
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/25985
                Categories
                Original Paper

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