title: Hydroxyfasudil ameliorates bladder dysfunction in male spontaneously hypertensive rats.
abstract: OBJECTIVE
  To investigate the effect of hydroxyfasudil, a nonselective Rho-kinase inhibitor, on hypertension-related bladder dysfunction in spontaneously hypertensive rats (SHRs), as there is an increasing evidence that the Rho-associated protein kinase (ROCK) system plays an important role in bladder contraction.
  
  
  METHODS
  Twelve-week-old male SHRs were treated with hydroxyfasudil (1 mg/kg i.p.) once a day for 6 weeks. Wistar rats and SHRs without treatment with hydroxyfasudil were used as controls. Six weeks after the hydroxyfasudil treatment, voiding functions were evaluated by metabolic cages and cystometric studies under urethane anesthesia (1.0 g/kg i.p.). Bladder blood flow (BBF) was estimated by the hydrogen clearance method. The bladder tissue levels of nerve growth factor (NGF) and ROCK activity were evaluated by the ELISA method.
  
  
  RESULTS
  The SHR showed significant increases in micturition frequency and decreases in single-voided volume in metabolic cages, and significantly increases in micturition frequency and intercontractile interval in cystometric studies. Furthermore, the SHR showed significant increases in the BBF and bladder NGF concentration compared with the Wistar rats. These alterations in the SHR were significantly ameliorated after treatment with hydroxyfasudil, with small changes in blood pressure. However, the maximum detrusor pressures during voiding and the ROCK activities in the experimental bladders were similar in all rats examined.
  
  
  CONCLUSIONS
  Our data indicate that this dose of hydroxyfasudil was effective on the BBF, whereas it had no significant effect on micturition pressure. These findings suggest that hydroxyfasudil could ameliorate hypertension-related bladder dysfunction in the SHR via improvement of the BBF (248 words).
authors.affiliation: Division of Urology, Tottori University School of Medicine, Yonago, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Inoue
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takenaka
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth; D020932:Nerve Growth Factor / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects*; D001743:Urinary Bladder / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: C431085:hydroxyfasudil; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D020932:Nerve Growth Factor; D054460:rho-Associated Kinases