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Effect of Naftopidil on Bladder Microcirculation in a Rat Model of Bladder Outlet Obstruction
Tsuyoshi Majima1, Tokunori Yamamoto1, Yasuhito Funahashi1
1Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Objectives:
To evaluate the effect of naftopidil on bladder capillary blood flow using bladder outlet obstruction model rats.
Methods:
Female Sprague-Dawley rats were divided into three groups: control group, bladder-outlet-obstruction group, and bladder-outlet-obstruction + naftopidil group. Bladder-outlet-obstruction surgery was performed in the bladder-outlet-obstruction and bladder-outlet-obstruction + naftopidil groups. The control group received sham-operation. The bladder-outlet-obstruction + naftopidil group were treated with naftopidil (30 mg/kg) for 14 days after bladder-outlet-obstruction operation, while the control and bladder-outlet-obstruction groups were treated with vehicle. Continuous cystometry was performed 14 days after the surgery. Bladder blood flow was measured after 14 days using a pencil lens charge-coupled device microscopy system. The bladder was then harvested for histology and measuring 8-hydroxy-2'-deoxyguanosine tissue level by enzyme-linked immunosorbent assay.
Results:
In cystometry, the bladder-outlet-obstruction rats showed bladder overactivity, while naftopidil treatment improved the cystometric pattern. The blood flow through the submucosal capillaries of the bladder base in the bladder-outlet-obstruction group was lesser than that in the control, whereas the bladder-outlet-obstruction + naftopidil group showed significantly greater blood flow than the bladder-outlet-obstruction group. The bladder tissue in the bladder-outlet-obstruction group showed a tendency to contain more hypertrophic detrusor muscle and inflammatory cells compared to those in the control group, while naftopidil treatment suppressed these histological changes. The 8-hydroxy-2'-deoxyguanosine levels in the bladder tissue significantly differed among the three groups (the bladder-outlet-obstruction group > the bladder-outlet-obstruction + naftopidil group > the control group).
Conclusions:
Naftopidil improved bladder overactivity as well as the impaired bladder blood flow.caused by bladder-outlet-obstruction.