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      Ethanol Inhibitory Effect on Rat Kidney Brush Border Aminopeptidases

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          Abstract

          Background/Aim: Confusing data have been reported about the effect of ethanol or its metabolic products on blood pressure. The pressor agent, angiotensin II (Ang II), is found to be susceptible to degradation by different enzymes known as angiotensinases. We have studied the effects of ethanol and L-NAME, an inhibitor of nitric oxide synthase, consumption on rat serum and kidney ectoenzymes: aminopeptidase N (APN) and aminopeptidase A (APA). Methods: Enzymatic activity of both enzymes was determined spectrophotometrically in serum and 10% homogenates of the rat kidney cortex using appropriate chromogenic substrates. Results: After 2 weeks of treatment with ethanol and L-NAME, blood urea and creatinine levels were significantly increased. The activities of APN (EC 3.4.11.2) and APA (EC 3.4.11.7) were reduced in serum as well as in kidney tissue during this period. L-NAME significantly attenuated activities of both enyzmes. Ethanol and L-NAME given simultaneously did not have an additional effect on the activity of investigated enzymes. Conclusion: Hypertension caused by chronic ethanol treatment as well as L-NAME administration could be associated with the reduction of APN and APA activity. Possible ethanol- and L-NAME-mediated inhibition of angiotensins degrading aminopeptidases could potentiate their effects on blood pressure.

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          Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glomerular damage.

          Tonic basal release of nitric oxide (NO) by vascular endothelial cells controls blood pressure (BP) in the basal state. In these studies we investigated the effects of chronic inhibition of basal NO synthesis in the rat for a 2-mo period. Significant systemic hypertension developed in chronically NO-blocked rats compared to controls. Marked renal vasoconstriction was also observed with elevations in glomerular blood pressure (PGC) and reductions in the glomerular capillary ultrafiltration coefficient (Kf). Chronically NO-blocked rats also develop proteinuria and glomerular sclerotic injury compared to controls. These studies therefore describe a new model of systemic hypertension with glomerular capillary hypertension and renal disease due to chronic blockade of endogenous NO synthesis. These observations highlight the importance of the endogenous NO system in control of normal vascular tone and suggest that hypertensive states may result from relative NO deficiency.
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            ALCOHOL-INDUCED HYPERTENSION

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              Elevations in plasma angiotensin II with prolonged ethanol treatment in rats.

              Chronic alcohol consumption frequently leads to hypertension in humans. While previous reports have implicated the renin-angiotensin system as a potential mediator of this effect, plasma angiotensin II (AII) levels were either not measured or yielded negative results. The present investigation noted significant elevations in circulating AII in rats intubated daily with ethanol (4 g/kg) for 50 days. Animals administered ethanol only once evidenced AII concentrations equivalent with water intubated controls. Radioligand binding assay data indicated no differences in the number or affinity of Sar1,Ile8-AII binding sites in the thalamus, septum-anterior ventral third ventrical region or adrenal gland comparing those groups chronically treated with ethanol to water intubated controls. These results may support a role for the vasoconstrictive hormone AII in the etiology of alcohol-induced hypertension.
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                Author and article information

                Journal
                NEE
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                1660-2129
                2007
                July 2007
                22 May 2007
                : 106
                : 3
                : e73-e76
                Affiliations
                aInstitute of Nephrology and Hemodialysis, Clinical Center Niš and bInstitute of Biochemistry, Medical Faculty, Niš, Serbia
                Article
                103019 Nephron Exp Nephrol 2007;106:e73–e76
                10.1159/000103019
                17519555
                787e4622-9787-42fe-aab2-df2fe9902386
                © 2007 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.

                History
                : 02 February 2007
                : 22 March 2007
                Page count
                Figures: 3, References: 28, Pages: 1
                Categories
                Minireview

                Cardiovascular Medicine,Nephrology
                Nephrotoxicity,Aminopeptidase N,Aminopeptidase A,Ethanol,<italic>L</italic>-NAME

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