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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      Differential Effects of Enalapril and Irbesartan in Experimental Papillary Necrosis

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          Abstract

          This study was undertaken to determine whether angiotensin receptor blockers are as renoprotective as angiotensin-converting enzyme inhibitors in an experimental model of chronic interstitial renal disease. Groups of rats received one of the following treatments for 1 week: (1) enalapril, (2) diltiazem, (3) a cocktail of hydralazine, reserpine, and hydrochlorothiazide, or (4) irbesartan (an AT<sub>1</sub> antagonist). The animals were injected with bromoethylamine (200 mg/kg), and antihypertensive treatment continued for 1 month. All drugs were effective in lowering the mean arterial pressure. The bromoethylamine-treated rats developed albuminuria and sustained a 40–50% decrease in creatinine clearance. Enalapril and irbesartan reduced albuminuria, but only enalapril partially prevented the decline in creatinine clearance and lowered the number of ED-1-positive cells. Diltiazem and cocktail had no effect on proteinuria, creatinine clearance, or ED-1 cells. In this experimental model, the effects of enalapril and irbesartan were not identical. Both drugs reduced proteinuria, but enalapril was more effective in protecting the renal function. The fact that the AT<sub>1</sub> antagonist protected against albuminuria but did not affect the clearance of creatinine implies that the results seen with angiotensin-converting enzyme inhibition may be in part due to an effect on angiotensin II via AT<sub>2</sub> receptor blockade or through an effect on bradykinin.

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          Determination of serum creatinine by a direct colorimetric method

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            ANTIHYPERTENSIVE DRUG TREATMENT IN CHRONIC RENAL ALLOGRAFT REJECTION IN THE RAT

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              Role of Kinins in the Renoprotective Effect of Angiotensin–Converting Enzyme Inhibitors in Experimental Chronic Renal Failure

              The aim of this study was to investigate whether the renoprotective effect of angiotensin–converting enzyme inhibitors (ACEIs) following 5/6 renal mass reduction is due in part to the potentiation of kinins. Three groups of rats with 5/6 renal mass reduction were studied during the 14 weeks following surgery. One group received no therapy (control); the second group was treated from the beginning with the ACEI ramipril (1 mg/kg/day) added to the drinking water, and the last group received ramipril plus a β 2 –bradykinin antagonist, HOE 140 (500 μg/kg/day) via osmotic minipumps. Plasma creatinine did not change in any group during the study. Urinary protein excretion rose in the controls from 9.18±1.6 to 45.0±5.6 mg/24 h at the end of the study. In ramipril group proteinuria was prevented (initial 7.5±1.0 and final 8.6±0.8 mg/24h). The effect of ramipril was abolished by HOE 140 (initial 11.6±2.0 and final 38.9±11 mg/ 24h). The systolic blood pressure of the controls increased from 106±2 to 144±5mmHg at the 14th week. Ramipril abolished the increase in systolic blood pressure. The effect of ramipril was reverted by HOE 140 (initial 108±2 and final 140±9 mmHg). Control rats had more severe histopathologic changes. Those animals receiving ramipril + HOE 140 displayed less severe glomerular changes, while rats treated only with ramipril had mild alterations. Thus the glomerular injury score was 2.11±0.32 for controls, 1.53±0.52 for rats treated with ramipril + HOE 140, and 0.06±0.04 for rats treated only with ramipril. The glomerular area was 20,886±1,410, 19,693±2,200 and 14,352±3,200 μm 2 , respectively, for the 3 groups. These results suggest that the protective effect of ACEIs in the development of chronic renal failure is partially mediated by kinins.
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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
                2001
                2001
                24 January 2001
                : 24
                : 1
                : 39-43
                Affiliations
                Divisions of Nephrology at aCook County Hospital, bUniversity of Illinois College of Medicine, cChicago VA Health Care System, and dHektoen Institute for Medical Research, Chicago, Ill., USA
                Article
                54204 Kidney Blood Press Res 2001;24:39–43
                10.1159/000054204
                11174005
                622a4f47-8a45-4395-982b-6eaf70935fed
                © 2001 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
                Page count
                Figures: 2, Tables: 3, References: 25, Pages: 5
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Angiotensin-converting enzyme inhibitors,Bromoethylamine,Papillary necrosis,AT1 antagonists

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