Objectives: To evaluate the antifibrotic role of captopril during ureteral scarring in a New Zealand rabbit model. Materials and Methods: The tissue expression and the fluctuation of EGF, TGF-β, FN, Col Ia1, Col Ia2 and Col III of the impaired ureter and the contralateral normal ureter were investigated by RT-PCR. The histological changes of the specimens were studied. When the sensitive markers had been selected, 10 New Zealand rabbits were randomly assigned to a captopril group and a control group. The specimens were harvested 2 weeks after the injury and then the histological examination and RT-PCR were performed. Results: By RT-PCR screening, EGF, TGF-β, FN, Col Ia1 and Col Ia2 were found to be significantly related to ureteral scarring (p < 0.05) confirmed by histological examination. The peak level of EGF, TGF-β and Col Ia1 appeared at 2 weeks after the injury, while for Fn and Col Ia2 it was at 3 and 4 weeks after the injury. An obvious reduction of fibrotic scarring was observed in the captopril group. The expression of EGF, Fn and Col Ia2 in the captopril group was significantly lower than in the control group (p < 0.05) after the treatment. Conclusions: EGF, TGF-β, Col Ia1, Col Ia2 and FN seemed to have an important role in the ureteral scarring after injury. Captopril might partially inhibit the fibrotic process by blocking the EGF, Col Ia2 and FN pathway so that it could be a promising treatment after ureteral injury.

Keywords:
Captopril, Ureteral injury, Fibrotic scarring, Cytokine
1.
Shirazi M, Khezri A, Samani SM, et al: Effect of intraurethral captopril gel on the recurrence of urethral stricture after direct vision internal urethrotomy: phase II clinical trial. IJU 2007;14:203–208.
2.
Mariotti G, Natale F, Trucchi A, et al: Ureteral injuries during gynecologic procedures. Minerva Urol Nephrol 1997;49:95–98.
3.
Assimos DG, Patterson LC, Taylor CL: Changing incidence and etiology of iatrogenic ureteric injuries. J Urol 1994;152:240.
4.
Kyung HK, Hyun CK, Mee YH, et al: The antifibrotic effect of TGF-b1 siRNAs in murine model of liver cirrhosis. Biochem Biophys Res Commun 2006;343:1072–1078.
5.
Zhang Z, Li X, Liu Y, et al: Recombinant human decorin inhibits cell proliferation and downregulates TGF-b1 production in hypertrophic scar fibroblasts. Burns 2007;33:634–611.
6.
Yen HC, Wan LC, Shun SC, et al: Expression of transforming growth factor-b1 and its receptors related to the ureteric fibrosis in rat model of obstructive uropathy. Urol 2000;163:1298–1303.
7.
Liu Jian-yi, Li Shi-rong, Ji Shu-xing: Pathological scars in the connective tissue growth factor gene expression. Repair and reconstruction. Chin J Surg 2003;17:436–438.
8.
Karakeçili AG, Satriano C, Gümüşderelioğlu M, Marletta G: Enhancement of fibroblastic proliferation on chitosan surfaces by immobilized epidermal growth factor. Acta Biomater 2008;4:989–996.
9.
Zoppi N, Barlati S, Colombi M: FAK-independent α-β3 integrin – EGFR comp lexes rescue from anoikismatrix – defective fibroblasts. Biochim Biophys Acta 2008;1783:1177–1188.
10.
Satish L, Babu M, Tran KT, Hebda PA, Wells A: Keloid fibroblast responsiveness to epidermal growth factor and activation of downstream intracellular signaling pathways. Wound Repair Regen 2004;12:183–192.
11.
Lee AR: Enhancing dermalmatrix regeneration and biomechanical properties of 2nd degree – burn wounds by EGF – impregnated collagen sponge dressing. Arch Pharm Res 2005;28:1311–1316.
12.
Mahmoud G, Ali M, Masoud S, et al: Antifibrotic effect of captopril and enalapril on paraquat-induced lung fibrosis in rats. J Appl Toxicol 2007;27:342–349.
13.
Kim MY, Baik SK, Park DH, et al: Angiotensin receptor blockers are superior to angiotensin-converting enzyme inhibitors in the suppression of hepatic fibrosis in a bile duct-ligated rat model. J Gastroenterol 2008;43:889–896.
14.
Wu HC, Liu HW, Cheng B, et al: Effect of angiotensin II receptors on collagen synthesis of fibroblasts derived from human hypertrophic scars. J Clin Rehab Tissue Eng Res 2009;13:2196–2200.
15.
Lee C, Guh J, Chen H, et al: Advanced glycation end-product-induced mitogenesis and collagen production are dependent on angiotensin II and connective tissue growth factor in NRK-49F cells. J Cell Biochem 2005;95:281–292.
16.
Peng H, Carretero O, Vuija N, et al: Angiotensin-converting enzyme inhibitors: a new mechanism of action. Circulation 2005;112:2436–2445.
17.
Pimentel J, Sundell C, Wang S, et al: Role of angiotensin II in the expression and regulation of transforming growth factor-a in obstructive nephropathy. Kidney Int 1995;48:1233–1246.
© 2012 S. Karger AG, Basel
2012
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.