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

Abstract

Objectives To investigate the effects of an alpha1‐adrenoceptor antagonist, silodosin, or a phosphodiesterase type 5 inhibitor, tadalafil, on bladder overactivity in spontaneously hypertensive rats. Methods Twelve‐week‐old male spontaneously hypertensive rats were perorally administered silodosin (100 µg/kg), tadalafil (2 or 10 mg/kg) or vehicle once daily for 6 weeks. 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. Results 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. Conclusions 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.

What is the real burden of the overactive bladder? Results from a national prevalence study

“…24 Vascular factors, such as high blood pressure, have been also involved in the physiopathology of OAB. 25 The possible mechanism is due to higher sympathetic activity in patients with OAB, which in turn leads to an increase in blood pressure. 26 An alternative mechanism involves changes in bladder vascularization.…”

Effects of tadalafil versus silodosin on voiding function in male patients with non‐neurogenic detrusor underactivity: A comparative study using propensity score matching

“…Several animal studies have reported that silodosin improved BBF in not only a BOO rat model, but also an atherosclerosis rat model, in induced chronic bladder ischemia and a spontaneously hypertensive rat model. 8,9,[16][17][18] Additionally, Yonekubo et al reported that silodosin improved voiding efficiency by increasing BBF in a diabetic cystopathy-associated DU rat model. 19 Goi et al reported that silodosin prevented the decrease in nerve distribution of the bladder and the increase in nerve growth factor expression by improving BBF in an atherosclerosis rat model, and ameliorated detrusor contractile function.…”

“…First, the increase in the BBF induced by both silodosin and tadalafil might contribute to the improvement of bladder function. Several animal studies have reported that silodosin improved BBF in not only a BOO rat model, but also an atherosclerosis rat model, in induced chronic bladder ischemia and a spontaneously hypertensive rat model 8,9,16–18 . Additionally, Yonekubo et al .…”

“…Recently, in a rat model with DU, an a1-blocker or PDE5 inhibitor increased blood perfusion to the pelvic organs, improved chronic bladder ischemia that induced fibrosis of the bladder wall, and protected both bladder function and morphology. [8][9][10][11] From these backgrounds, the present study aimed to investigate the comparative efficacy for non-neurogenic DU over a 12-month period of two standard pharmacological therapies for male LUTS: a PDE5 inhibitor (tadalafil) and an a1-blocker (silodosin). We assessed the change in storage and voiding functions, in addition to the change in LUTS using subjective symptom questionnaire, in men with LUTS caused by nonneurogenic DU.…”

“…As far as we know, no study has focused on the efficacy of these drugs on bladder function including bladder contractility or on subjective symptoms for male patients with non‐neurogenic DU. Recently, in a rat model with DU, an α1‐blocker or PDE5 inhibitor increased blood perfusion to the pelvic organs, improved chronic bladder ischemia that induced fibrosis of the bladder wall, and protected both bladder function and morphology 8–11 . From these backgrounds, the present study aimed to investigate the comparative efficacy for non‐neurogenic DU over a 12‐month period of two standard pharmacological therapies for male LUTS: a PDE5 inhibitor (tadalafil) and an α1‐blocker (silodosin).…”