Back to Journals » Research and Reports in Urology » Volume 10

Effect of angiotensin II receptor blocker on TGF-β1, MMP-1, and collagen type I and type III concentration in New Zealand rabbit urethral stricture model

Authors Siregar S, Farenia R, Sugandi S, Roesli RM

Received 8 September 2017

Accepted for publication 26 April 2018

Published 2 October 2018 Volume 2018:10 Pages 127—133

DOI https://doi.org/10.2147/RRU.S151209

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Jan Colli


Safendra Siregar, Reni Farenia, Suwandi Sugandi, Rully M Roesli

Urology Division, Department of Surgery, Hasan Sadikin Hospital Bandung, Faculty of Medicine Padjadjaran University, Bandung, Indonesia

Introduction: Urethral stricture is a disease with a high recurrence rate. Angiotensin II via AT1 receptor increases collagen formation through its effects on TGF-β1 and inhibition of collagenase activity. In this study, we evaluated the antifibrotic effect of angiotensin II receptor blocker on urethral stricture formation by creating a urethral stricture model in a male rabbit.
Material and methods: Thirty three male adult rabbits were separated into 3 groups (control, treatment, and sham). Group I consisted of 15 rabbits with urethral stricture that did not undergo any treatment, group II consisted of 15 rabbits with urethral stricture that were treated with a daily dose of 15 mg/kg losartan, given orally. Group III consisted of 3 rabbits with normal urethra and without any treatment. After 1, 2, and 4 weeks, the urethral tissues were collected, processed, and examined for TGF-β1, MMP-1, collagen type I, and collagen type III using enzyme-linked immunosorbent assay. Data were analyzed using 2-way analysis of variance using SPSS version 20.0.
Results: Urethral TGF-β1 concentration in the treatment group was significantly lower during the 2nd and 4th week of observation (p<0.0001), MMP-1 was significantly higher in the 1st, 2nd, and 4th week of observation (p<0.0001), collagen type I was significantly lower during the 2nd (p=0.001) and 4th week (p<0.0001), and collagen type III concentration was significantly lower in the 2nd and 4th week of observation (p<0.0001).
Conclusion: Angiotensin II receptor blocker could limit the progression of urethral stricture. The mechanism may be related to the AT1 blockage that leads to a decrease in TGF-β1 concentration, eventually resulting in lower collagen concentration due to increased MMP-1 activity.

Keywords: angiotensin receptor blocker, collagen, MMP-1, TGF-β1, urethral stricture

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]