Hydroxyfasudil ameliorates bladder dysfunction in male spontaneously hypertensive rats

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.

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.

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.

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).