Hiroko Okutsu

Effects of Tamsulosin on Bladder Blood Flow and Bladder Function in Rats With Bladder Outlet Obstruction

OBJECTIVES To investigate the mechanism underlying the ameliorating effect of tamsulosin, an alpha(1)-adrenoceptor antagonist, on storage symptoms associated with benign prostatic hyperplasia, the effects of tamsulosin on bladder blood flow (BBF) and bladder function was evaluated in rats with bladder outlet obstruction (BOO). METHODS BOO was produced by partial ligature of the proximal urethra, which was maintained for 2 weeks. Tamsulosin was subcutaneously administered via an osmotic pump for 2 weeks immediately after the BOO surgery. The BBF in the sham-operated rats, the control BOO rats, and the tamsulosin-treated BOO rats was measured using the fluoromicrosphere method. Each rat was kept in a metabolic cage for observation of micturition behavior. Expression of the alpha(1)-adrenoceptor subtype mRNA in the vesical artery was measured by reverse transcriptase-polymerase chain reaction. RESULTS BBF was significantly reduced in BOO rats compared with sham-operated rats, and tamsulosin significantly increased the BBF in BOO rats. Tamsulosin ameliorated the decrease in mean voided volume in BOO rats with bladder masses < 500 mg. Expression of the alpha(1)-adrenoceptor subtype in the vesical artery was alpha(1a)- > alpha(1d)-adrenoceptors; almost no expression was observed of alpha(1b)-adrenoceptors in either sham-operated or BOO rats. CONCLUSIONS Tamsulosin increased BBF in BOO rats via an antagonistic effect, presumably on the alpha(1A)- and/or alpha(1D)-adrenoceptor in the vesical artery mainly, and improved the decrease in mean voided volume. Therefore, the results of this study suggest that tamsulosin improves bladder overactivity via improvement of BBF.

Effect of Tamsulosin on Bladder Blood Flow and Bladder Function in a Rat Model of Bladder Over Distention/Emptying Induced Bladder Overactivity

PURPOSE Decreased bladder blood flow was the subject of a recent study as a pathophysiological cause of bladder overactivity. We developed a rat model of bladder over distention/emptying induced bladder overactivity and investigated the effect of the α(1)-adrenoceptor antagonist tamsulosin on bladder blood flow and bladder function in this model. MATERIALS AND METHODS The bladder was distended with 2 ml saline using anesthesia for 2 hours (over distention) and then emptied. Bladder blood flow was measured using a perfusion imager. Micturition behavior and parameters were observed using a metabolic cage and a cystometry method, respectively, from 2 hours after bladder emptying. After model establishment was confirmed we examined the participation of afferent C-fibers and the effects of tamsulosin in rats pretreated with capsaicin (Sigma-Aldrich®) (125 mg/kg) and tamsulosin (1 μg/kg per hour), respectively, using a metabolic cage. RESULTS Decreased bladder blood flow was observed upon over distention with partial recovery at emptying. Bladder over distention/emptying increased micturition frequency and decreased mean voided volume in the micturition recording study, and decreased the intercontraction interval and voided volume without affecting micturition pressure, threshold pressure or post-void residual volume in the cystometry study. Capsaicin pretreatment did not affect bladder overactivity. However, 1-week continuous treatment with tamsulosin increased bladder blood flow after bladder emptying, resulting in decreased micturition frequency and increased voided volume. CONCLUSIONS Bladder over distention/emptying induced bladder blood flow decrease/partial recovery and caused bladder overactivity via a mechanism other than capsaicin sensitive C-fiber activation. Findings in tamsulosin treated rats confirmed the potency of tamsulosin to increase bladder blood flow and ameliorate bladder overactivity.

Effect of tamsulosin on bladder microcirculation in a rat ischemia-reperfusion model, evaluated by pencil lens charge-coupled device microscopy system.

OBJECTIVES To investigate the effect of tamsulosin hydrochloride on bladder microcirculation in a rat ischemia-reperfusion model using a pencil lens charge-coupled device microscopy system (PLCMS). METHODS Changes in blood flow through a submucosal capillary of the rat bladder were measured during bladder filling using the PLCMS. One week after starting infusion of either physiological saline or tamsulosin, blood flow in the bladder was halted by bladder overdistention via an infusion of physiological saline. The bladder was then emptied to be reperfused with blood. Changes in blood flow through a submucosal capillary of the bladder during ischemia and reperfusion were measured using a PLCMS, and the data obtained for the control group and tamsulosin group were compared. RESULTS As the bladder was distended, the velocity of red blood cell flow in a submucosal capillary of the bladder slowed and stopped altogether when the bladder became overdistended. In the control group, capillary blood flow improved over time after release from overdistention but failed to return to the baseline level, demonstrating that reperfusion injury to bladder microcirculation was caused by bladder overdistention and emptying. In the tamsulosin group, capillary blood flow rapidly returned to baseline after release from overdistention. CONCLUSIONS Using a PLCMS, bladder microcirculation was able to be visualized and quantitatively assessed by measuring the velocity of blood flow in a submucosal capillary of the bladder. Findings from the present study suggest that tamsulosin hydrochloride exerts a protective effect on blood flow in ischemia-reperfusion injury of the bladder.

ESTABLISHMENT OF A BLADDER ISCHEMIA/REPERFUSION- INDUCED BLADDER OVERACTIVITY MODEL AND THE EFFECTS OF TAMSULOSIN ON BLADDER BLOOD FLOW AND BLADDER FUNCTION IN THAT MODEL

Hypothesis / aims of study Patients with benign prostatic hyperplasia (BPH) are known to show both voiding and storage symptoms. α1-Adrenoceptor antagonists, which are widely-used as a BPH therapy, reportedly improve not only voiding symptoms in patients with BPH, but storage symptoms as well. Bladder outlet obstruction (BOO) is widely thought to contribute to voiding symptoms; therefore, relaxation of the urethra and prostate via blockade of α1-adrenoceptors may be the main mechanism by which voiding function can be improved. Because storage symptoms are multifactorial, neither the mechanism responsible for the storage symptoms induced by BOO, nor that behind the improvement in symptoms seen with α1-adrenoceptor antagonists are clearly understood. In this study, focus was placed on bladder blood flow as one of the possible mechanisms causing the storage symptoms. To examine the influence of bladder ischemia / reperfusion on bladder function, a bladder ischemia / reperfusion model was established in rats. In addition, the effect of tamsulosin, the most common α1-adrenoceptor antagonist, on bladder function was examined in this model.