Effect of the rho-kinase inhibitor hydroxyfasudil on bladder overactivity: an experimental rat model.
OBJECTIVE
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 microM 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.
Masago
Toshihiko
T
Department of Surgery, Division of Urology, Tottori University Faculty of Medicine, Yonago, Tottori, Japan.
Watanabe
Takeshi
T
Saito
Motoaki
M
Kinoshita
Yukako
Y
Sato
Keisuke
K
Miyagawa
Ikuo
I
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
C431085:hydroxyfasudil; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases