Premium
Effect of the rho‐kinase inhibitor hydroxyfasudil on bladder overactivity: An experimental rat model
Author(s) -
Masago Toshihiko,
Watanabe Takeshi,
Saito Motoaki,
Kinoshita Yukako,
Sato Keisuke,
Miyagawa Ikuo
Publication year - 2009
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/j.1442-2042.2009.02375.x
Subject(s) - medicine , carbachol , overactive bladder , urology , intraperitoneal injection , pharmacology , pathology , alternative medicine , stimulation
Objectives: To investigate the effects of the rho‐kinase inhibitor hydroxyfasudil on bladder overactivity in cyclophosphamide (CYP)‐induced cystitis. Methods: Female Sprague–Dawley rats received a single intraperitoneal injection of CYP (200 mg/kg). Four days later, bladder function was evaluated by: (i) monitoring micturition behavior in metabolic cages between hydroxyfasudil‐ and vehicle‐treated animals; (ii) measuring changes in continuous cystometrograms in response to intravenous hydroxyfasudil under anesthesia; and (iii) conducting a functional study examining the effect of hydroxyfasudil on the concentration‐response curves to carbachol in bladder tissue strips. Results: Intraperitoneal injection of hydroxyfasudil (10 mg/kg) significantly increased both the average and maximal voided volumes. Hydroxyfasudil significantly decreased the maximal detrusor pressure, whereas the intercontraction interval was not significantly affected. After administration of 0.1, 0.3, 1, and 3 µM hydroxyfasudil, the maximal contraction of the concentration‐response curves to carbachol was significantly reduced to 74.5 ± 4.2%, 55.2 ± 5.6%, 29.4 ± 5.6%, and 21.6 ± 8.2% of the control values, respectively. Conclusions: The present findings indicate that hydroxyfasudil might be a new treatment option for CYP‐induced detrusor overactivity.