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Effects of Oral Rho Kinase Inhibitor Fasudil on Detrusor Overactivity after Bladder Outlet Obstruction in Rats

Authors

  • Ji-Yoon KIM,

    1. Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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  • Ji-Yeon HAN,

    1. Department of Urology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
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  • Tae Gyun KWON,

    1. Genitourinary Cancer Center, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Korea.
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  • Myung-Soo CHOO

    Corresponding author
    1. Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
      Myung-Soo Choo, MD, PhD, Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songap-gu 138-736, Seoul, Korea. Tel: +82-2-301-3735; Fax: +82-2-477-8928. Email: mschoo@amc.seoul.kr
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Myung-Soo Choo, MD, PhD, Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songap-gu 138-736, Seoul, Korea. Tel: +82-2-301-3735; Fax: +82-2-477-8928. Email: mschoo@amc.seoul.kr

Abstract

Objectives: Bladder outlet obstruction (BOO)-related detrusor hypertrophy is associated with upregulation of Rho-kinase (ROCK) activity in an experimental animal model, and has been implicated in BOO-induced bladder dysfunction. The aim of this study was to test whether chronic oral administration of an oral ROCK inhibitor, fasudil (HA1077, 5-isoquinolinesulfonyl homopiperazine), could prevent the development of both detrusor hypertrophy and detrusor overactivity in rat model.

Methods: Thirty five-week-old male Sprague-Dawley rats were divided into three groups (n = 10 per group): control (sham surgical) with no treatment (group 1); 6-week obstructed rats (group 2); and 6-week obstructed rats treated for 6 weeks with fasudil (group 3).

Results: The BOO group showed increased detrusor overactivity. Treatment with fasudil partly but significantly ameliorated the development of detrusor overactivity. The expression of RhoA protein in detrusor muscle was significantly greater in the BOO group than in the control group and subsequently decreased with fasudil treatment in the BOO-induced rat.

Conclusion: These findings suggest that fasudil, a specific inhibitor of Rho-kinase, ameliorates BOO-induced detrusor overactivity in a rat model. Thus, ROCK inhibitor might be used as a novel agent to treat overactive bladder symptoms.

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