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      Beneficial Effect of the Long-Term Treatment with the Combination of an ACE Inhibitor and a Calcium Channel Blocker on Renal Injury in Rats with 5/6 Nephrectomy

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          Abstract

          The effects of the addition of a calcium channel blocker, verapamil (20 mg/kg/day) to an ACE inhibitor, trandolapril (0.7 mg/kg/day) in a 6-month treatment on renal insufficiency development in rats with 5/6th nephrectomy, were studied. Every month we measured heart rate and arterial pressure by the tail-cuff method. Renal function studies were performed in metabolic cages. At the end of the study, renal tissue was prepared for light microscope analysis. Renal lesions were assessed by semiquantitative scores in a blind fashion. Corpuscular section area, intraglomerular and tubulointerstitial fibrosis were determined by digital image analysis with a specific software (Fibrosis HR<sup>®</sup>) on syrium red-stained renal sections. Trandolapril markedly increased the survival ratio that after 6 months reached 87% in comparison with 61% in untreated rats. No mortality was observed in rats treated with the combination of verapamil and trandolapril. Trandolapril treatment prevented the development of hypertension. The combination verapamil-trandolapril did not induce further reduction on blood pressure. The untreated group showed a marked proteinuria, that in the trandolapril group showed an important reduction. The verapamil + trandolapril group showed a proteinuria significantly smaller than that of all the other groups. Light microscopy semiquantitative studies of the renal injury showed that the trandolapril and verapamil + trandolapril groups had a marked reduction in glomerular and tubulointerstitial alterations, compared with untreated animals. Quantitative determinations of glomerular and interstitial fibrosis performed on syrium red-stained renal sections demonstrated that fibrosis was reduced when rats when treated with trandolapril and even more with verapamil + trandolapril when they were compared to untreated animals’ values. In conclusion, long-term treatment with verapamil given in addition to trandolapril produces additional protection against progressive renal injury associated to subtotal nephrectomy.

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          Calcium antagonists and renal protection. Current status and future perspectives.

          During the past decade, considerable attention has been focused on the effects of calcium antagonists on renal function. Direct in vivo and in vitro observations in diverse experimental models indicate that calcium antagonists antagonize preglomerular vasoconstriction. Furthermore, calcium antagonists are postulated to have additional properties that contribute to their ability to afford renal protection. These putative mechanisms include the ability to retard renal growth, and possibly to attenuate mesangial entrapment of macromolecules, and to attenuate the mitogenic effects of diverse growth factors. Although the clinical implications of the above-mentioned findings have not been fully delineated, the results of recent clinical trials indicate that calcium antagonists exert salutary effects on renal function in clinical settings characterized by impaired renal hemodynamics, including transplant-associated acute renal insufficiency and, possibly, cyclosporine nephrotoxicity. Evidence has accrued suggesting that calcium antagonists may also be protective against acute radiocontrast-induced nephrotoxicity. Finally, the renal hemodynamic and natriuretic effects of calcium antagonists commend their use as antihypertensive agents in the management of essential hypertension, renovascular hypertension, and transplant-associated hypertension.
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            Author and article information

            Journal
            EXN
            Nephron Exp Nephrol
            10.1159/issn.1660-2129
            Cardiorenal Medicine
            S. Karger AG
            1660-2129
            1998
            February 1998
            04 February 1998
            : 6
            : 1
            : 39-49
            Affiliations
            Instituto Reina Sofía de Investigación Nefrológica, Departments of a Physiology and Pharmacology, and b Histology, Faculty of Medicine, University of Salamanca, Spain
            Article
            20503 Exp Nephrol 1998;6:39–49
            10.1159/000020503
            © 1998 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: 7, Tables: 3, References: 44, Pages: 11
            Product
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/20503
            Categories
            Original Paper

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