Protective Effect of a Rho-kinase Inhibitor on Bladder Dysfunction in a Rat Model of Chronic Bladder Ischemia

Abstract

Objective: To investigate the effect of fasudil, a Rho-kinase inhibitor, on chronic ischemia-related bladder dysfunction.

Materials and methods: Male Sprague-Dawley rats (16 weeks old) were divided into control, chronic bladder ischemia (CBI), and CBI with fasudil treatment (CBI-Fa) groups. The CBI and CBI-Fa groups underwent balloon endothelial injury of bilateral iliac arteries and received a 2% cholesterol diet for 8 weeks after the procedure to induce CBI. The CBI-Fa group was given oral fasudil (30 mg/kg/day) using zonde for 8 weeks after the procedure. The control group received a regular diet for 8 weeks. After cystometry in a conscious state, rats from each group were euthanized, and the bladders and common iliac arteries were harvested for pharmacologic and histologic examination.

Results: Mean wall thickness of the common iliac arteries was significantly greater in the CBI group than in controls. Contractile responses of muscle strips were significantly lower in CBI group rats than in controls. In the CBI group, micturition interval was significantly shorter, and bladder capacity was significantly lower compared with those in controls. In the CBI-Fa group, arterial wall thickening was significantly suppressed compared with the CBI group. Significant improvements in muscle strip contractility and cystometric parameters were seen in the CBI-Fa group compared with the CBI group.

Conclusion: Our results suggest that chronic treatment with fasudil could prevent neointimal formation in arteries and bladder dysfunction in this rat model. Fasudil may be therapeutically useful in protecting bladder function in chronically ischemic bladders.