281 EFFECT OF NAFTOPIDIL ON BLADDER MICROCIRCULATION IN A BLADDER OUTLET OBSTRUCTION RAT MODEL: EVALUATION WITH A PENCIL LENS CHARGE-COUPLED DEVICE MICROSCOPY SYSTEM

Abstract

INTRODUCTION AND OBJECTIVES: Patients with benign prostatic hyperplasia (BPH) show both voiding and storage symptoms. ƒ?-Adrenoreceptor antagonists, including naftopidil, are reported to improve both voiding and storage symptoms. However, the mechanism underlying bladder outlet obstruction (BOO)-induced storage symptoms and that underlying the symptom improvement seen with ƒ?adrenoreceptor antagonists are not clearly understood. Some reports have presented that bladder blood flow may be one of the factors responsible for the mechanism. This study focused on bladder microcirculation as a possible mechanism underlying storage symptoms. The effect of naftopidil on bladder capillary blood flow was evaluated using BOO model rats. METHODS: The study included 7-week-old female SpragueDawley rats, which were divided into 3 groups: sham group, wherein the rats underwent a sham operation and 14-day vehicle treatment; BOO group, wherein the BOO model rats underwent an operation to establish partial BOO and a 14-day vehicle treatment; and the naftopidil group, wherein the BOO rats underwent an operation to establish partial BOO and a 14-day naftopidil treatment (30 mg/kg). Voiding functions were evaluated by voiding behavior analysis and cystometric studies. Bladder blood flow was measured using the pencil lens charge-coupled device (CCD) microscopy system (PLCMS). The level of 8-hydroxy-2ui-deoxyguanosine (8-OHdG), an oxidative stress biomarker, was measured in bladder tissue by using an enzyme-linked immunosorbent assay. RESULTS: The results of both voiding behavior analysis and cystometric studies showed that the BOO group rats had significantly greater micturition frequency than the sham group rats and that the naftopidil group rats had a significantly longer micturition interval than the BOO group rats. The blood flow through the submucosal capillaries of the bladder in the BOO group rats was lesser than that in the sham group rats, whereas the naftopidil group rats showed significantly greater blood flow than the BOO group rats. The 8-OHdG levels in the bladder tissue significantly differed among the 3 groups (BOO group naftopidil group sham group). CONCLUSIONS: The results of this study show that naftopidil reduces the BOO-induced bladder overactivity and improves the impaired bladder blood flow caused by BOO.