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      Treatment with a Ca 2+ Channel Blocker, Barnidipine, Reduces Platelet-Derived Growth Factor B-Chain mRNA in Glomeruli of Spontaneously Hypertensive Rats

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          Abstract

          We investigated the effect of barnidipine hydrochloride, a Ca<sup>2+</sup> channel blocker, on the glomerular level of mRNA expression of platelet-derived growth factor (PDGF) B-chain and transforming growth factor (TGF)-β<sub>1</sub> in spontaneously hypertensive rats (SHR) with reverse transcription and polymerase chain reaction. Thirteen-week-old SHR were provided with food containing barnidipine (0.6 mg/g of food, average dose during treatment: 53 mg/kg of body mass/day) for 3 weeks. A stable reduction in systolic blood pressure relative to that of age-matched control SHR was recorded after week 1 of therapy. Although no renal histological changes were observed after 3 weeks of treatment with barnidipine, the level of expression of PDGF B-chain mRNA in glomeruli was significantly reduced relative to that in control SHR. The glomerular level of TGF-β<sub>1</sub> mRNA expression was not affected by the treatment. Treatment with barnidipine significantly reduced the excretion of urinary protein. Thus, the stable reduction in systemic blood pressure by barnidipine is associated with a reduction in PDGF B-chain mRNA expression in the glomerulus and reduction in urinary protein excretion in SHR.

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          Antihypertensive treatment of patients with proteinuric renal diseases: risks or benefits of calcium channel blockers?

          F Huysmans, H Kloke, J Wetzels … (1998)
          In patients with proteinuric renal diseases the rate of progression of renal insufficiency is determined by the level of blood pressure and proteinuria. It has been demonstrated that strict blood pressure control with angiotensin converting enzyme (ACE)-inhibitors or beta-blockers, aimed at reaching values below 130/80 mm Hg, attenuates the deterioration of renal function. In general, the beneficial effects of these drugs are reflected in a parallel lowering of proteinuria. Calcium channel blockers are effective antihypertensive drugs, however, their safety in patients with proteinuric renal diseases and renal insufficiency may be questioned because of reported untoward effects on urinary protein excretion. The present review discusses the potential benefits and risks of calcium channel blockers (CCBs) in the treatment of patients with renal diseases. To this end we have evaluated the effects of these drugs in animal models of progressive renal injury. In these animal models adverse effects of CCBs have been reported which are attributed to an impairment of autoregulation. In patients with proteinuria, the dihydropyridine CCBs do not lower proteinuria despite a reduction of blood pressure. Studies on the effects on the course of renal function are limited, however, the available data do suggest that this class of CCBs may be less advantageous than other antihypertensive drugs, thus arguing against the use of these agents as first-line drugs in patients with proteinuric renal diseases. Information on the effects of the non-dihydropyridine CCBs is limited to a small number of studies in patients with diabetic renal disease. Although the data suggest that these classes of CCBs might be more beneficial, more studies are needed, particularly in patients with non-diabetic renal diseases, before founded conclusions can be reached.
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            Effects of treatment with angiotensin‐converting enzyme inhibitor (ACEI) or angiotensin II receptor antagonist (AIIRA) on renal function and glomerular injury in subtotal nephrectomized rats

            Masatoshi Yamamoto, Mitsumine Fukui, Ichiyu Shou … (1998)
            The aim of this study was to determine if treatment with angiotensin‐converting enzyme inhibitors (ACEI) or angiotensin II receptor antagonists (AIIRA) might decrease urinary albumin excretion and prevent glomerular enlargement and glomerulosclerosis in subtotal (5/6) nephrectomized rats. Morphometric image analysis of glomeruli was also performed in the subtotal nephrectomized rats. The nephrectomized rats were treated with ACEI (enalapril 100mg/l), AIIRA (L‐158,809 10 mg/l) or TRX (reserpine 5 mg/l, hydralazine 80 mg/l, and hydrochlorothiazide 25 mg/l) and euthanized at 16 weeks after renal ablation. Treatments were started at 2 weeks (early treatment: Group I) or 8 weeks (later treatment: Group II) after the ablation. ACEI and AIIRA treatments were equally and significantly effective in limiting albuminuria and progression of glomerular sclerosis. TRX was also as effective in decreasing urinary albumin excretion and preserving the renal function as ACEI or AIIRA in Group I. The improvement of albuminuria, glomerular enlargement and sclerosis after these treatments in Group II was significantly less than that in Group I. It appears that the early treatment with angiotensin converting enzyme inhibitor, angiotensin II receptor antagonist or reserpine, hydralazine and hydrochlorothiazide (TRX) may prevent glomerular injury in human patients with renal hypertension. J. Clin. Lab. Anal. 11:53–62. © 1997 Wiley‐Liss, Inc.
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              Inhibitory effects of antihypertensive drugs on mesangial cell proliferation after anti-thymocyte serum (ATS) — induced mesangiolysis in spontaneously hypertensive rats

              S Kiyama, F Nanishi, S. Tomooka … (1994)
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                Author and article information

                Journal
                Journal ID (publisher-id): AJN
                Journal ID (nlm-ta): Am J Nephrol
                Journal ID (doi): 10.1159/issn.0250-8095
                Title: American Journal of Nephrology
                Publisher: S. Karger AG
                ISSN (Print): 0250-8095
                ISSN (Electronic): 1421-9670
                Publication date Subscription-year: 1999
                Publication date (Print): October 1999
                Publication date (Electronic): 26 November 1999
                Volume: 19
                Issue: 5
                Pages: 615-621
                Affiliations
                aThird Department of Medicine, Okayama University Medical School, bHealth and Medical Center and cFaculty of Education, Okayama University, Okayama, Japan
                Article
                Publisher ID: 13511 Other ID: Am J Nephrol 1999;19:615–621
                DOI: 10.1159/000013511
                PubMed ID: 10575194
                SO-VID: 609a2a70-e8a8-48d0-849e-59f5e2df5672
                Copyright © © 1999 S. Karger AG, Basel
                License:

                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: 4, Tables: 3, References: 34, Pages: 7
                Categories
                Subject: Laboratory Investigation

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Spontaneously hypertensive rat,Glomerulus,PDGF B-chain,Calcium channel blocker,Barnidipine hydrochloride,Hypertensive nephropathy
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Spontaneously hypertensive rat, Glomerulus, PDGF B-chain, Calcium channel blocker, Barnidipine hydrochloride, Hypertensive nephropathy

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