The effects of a selective noradrenaline reuptake inhibitor on the urethra: An in vitro and in vivo study

Objective: To identify the effects of a selective noradrenaline reuptake inhibitor (venlafaxine) on urethral perfusion pressure (UPP) in rabbits and rats, and thus assess its therapeutic potential for treating stress urinary incontinence. Materials and methods: Strips of bladder and proximal urethra were prepared from female New Zealand White rabbits. Each strip was electrically stimulated and the contractile responses of controls strips compared with those after pretreatment with venlafaxine (100 μmol/L). In separate experiments using 80 adult female Sprague-Dawley rats (250-300 g), changes in intravesical pressure and UPP after the intra-arterial and intra-urethral administration of phenylephrine, phentolamine, fluoxetine and venlafaxine were monitored using double-lumen catheters. Results: Pretreatment with venlafaxine significantly decreased the contraction of bladder strips (P=0.01) and significantly increased the contraction of urethral strips (P=0.008). In vivo, phenylephrine administered by both routes significantly increased UPP (P=0.02); phentolamine (arterial) significantly decreased UPP (P=0.001); fluoxetine (arterial) had no effect on UPP, and venlafaxine (both routes) significantly increased UPP (both P<0.001). The intravesical pressure was not changed significantly in any animal. Conclusions: Venlafaxine effectively increased UPP both in vitro and in vivo; these results imply that venlafaxine may be useful for treating stress urinary incontinence, by increasing the UPP.