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      Alteration of Endothelin-1 Concentration in STZ-Induced Diabetic Rat Nephropathy

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          Abstract

          Background: Recently, an endothelin (ET-1) with a potent vasoconstrictive activity and stimulative activity of vascular muscular cell growth was discovered and blood ET-1 levels were higher in diabetic patients than in healthy subjects, suggesting that high ET-1 levels assist development and progression of diabetic microangiography. Methods: We examined renal function, and serum and tissue ET-1 levels in streptozotocin (STZ)-induced diabetic rats treated with a prostaglandin (PG) I<sub>2</sub> derivative to investigate the effect of PGI<sub>2</sub> in diabetic vascular disturbance. Results: Renal weight, urinary albumin, urinary N-acetyl-β, D-glucosaminidase (NAG) and serum ET-1 levels increased in STZ-induced diabetic rats, and a tendency to increase in renal tissue ET-1 levels was observed. Furthermore, electron-microscopic findings in the kidneys showed mesangial cell proliferation and mesangial matrix expansion which might be caused by diabetic nephropathy. The PGI<sub>2</sub> derivative reduced urinary albumin and NAG levels in STZ-induced rats. It was considered, therefore, that the PGI<sub>2</sub> derivative is effective in diabetic nephropathy. As the PGI<sub>2</sub> derivative also reduced renal tissue ET-1 levels, improvement of diabetic nephropathy partially was considered to result from the reduction of renal tissue ET-1 levels. Conclusion: In STZ-induced rats, increased serum ET-1 levels and a tendency to increase in renal tissue ET-1 levels were associated with increases in urinary albumin and NAG levels, and these levels were decreased by a PGI<sub>2</sub> derivative. These findings suggested that increased ET-1 concentrations assist development and progression of diabetic nephropathy, especially diabetic microangiopathy, and the PGI<sub>2</sub> derivative may be effective for inhibition of diabetic microangiopathy mediated by reduction of ET-1 concentrations.

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          Most cited references 3

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          Cloning and sequence analysis of cDNA encoding the precursor of a human endothelium-derived vasoconstrictor peptide, endothelin: Identity of human and porcine endothelin

          A cDNA encoding a human endothelium-derived vasoconstrictor peptide, endothelin, was isolated from a human placenta cDNA library. The nucleotide sequence of this cDNA clone showed that the primary structure of the human preproendothelin has 212 amino acid residues and is highly homologous to porcine preproendothelin, and that human endothelin is identical with porcine endothelin.
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            Presence of immunoreactive endothelin in human plasma.

             Y Hirata,  T. Emori,  K Ando (1989)
            A highly specific and sensitive radioimmunoassay has been established for measurement of human endothelin (hET) in human plasma. After extraction of plasma with an octyl-silica column, this assay allowed for detection of immunoreactive (IR) hET as low as 0.2 fmol/ml. In 16 healthy subjects, the mean concentration of plasma IR-hET was 0.6 fmol/ml. Reverse-phase HPLC coupled with radioimmunoassay revealed two major IR-hET components, one corresponding to authentic hET(1-21) and another with more hydrophilicity than hET(1-21). These data indicate that ET is a circulating vasoconstrictor hormone in man.
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              A thromboxane A2 synthetase inhibitor retards hypertensive rat diabetic nephropathy

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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2001
                2001
                14 March 2002
                : 56
                : 5-6
                : 165-171
                Affiliations
                Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
                Article
                48113 Horm Res 2001;56:165–171
                10.1159/000048113
                11910202
                © 2002 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: 1, Tables: 3, References: 30, Pages: 7
                Categories
                Original Paper

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