Effects of silodosin and tadalafil on bladder dysfunction in spontaneously hypertensive rats: Possible role of bladder blood flow.

Abstract

To investigate the effects of an alpha1-adrenoceptor antagonist, silodosin, or a phosphodiesterase type5 inhibitor, tadalafil, on bladder overactivity in spontaneously hypertensive rats. Twelve-week-old male spontaneously hypertensive rats were perorally administered silodosin (100µg/kg), tadalafil (2 or 10mg/kg) or vehicle once daily for 6weeks. Wistar rats were used as normotensive controls and were treated with the vehicle. At 18-weeks-old, the effects of silodosin or tadalafil on blood pressure, bladder blood flow, urodynamic parameters (i.e. micturition frequency, urine output, inter-contraction interval, maximum voiding pressure, single voided volume and post-voiding residual urine volume), and bladder tissue levels of malondialdehyde, interleukin-6 and tumor necrosis factor-alpha were measured. A significant increase in blood pressure, micturition frequency and bladder tissue levels of malondialdehyde, interleukin-6 and tumor necrosis factor-alpha was noted in spontaneously hypertensive rats. The single voided volume, bladder capacity and bladder blood flow were significantly lower in the spontaneously hypertensive rats than in the Wistar rats. Treatment with silodosin and the higher dose of tadalafil improved the urodynamic parameters, bladder blood flow and bladder tissue levels of malondialdehyde in the spontaneously hypertensive rats without affecting the blood pressure and bladder tissue levels of interleukin-6 and tumor necrosis factor-alpha. Treatment with silodosin or tadalafil might improve hypertension-related bladder overactivity, as shown in spontaneously hypertensive rats through an improvement in the bladder blood flow and bladder tissue levels of oxidative stress.