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 inh ibitor (ventafaxine) on urethral perfusion pressure (UPP) in rabbits and ra ts, and thus assess its therapeutic potential for treating stress urinary i ncontinence. Materials and methods Strips of bladder and proximal urethra were prepared from female New Zealand White rabbits. Each strip was electrically stimulat ed and the contractile responses of controls strips compared with those aft er pretreatment with venlafaxine (100 mu mol/L). In separate experiments us ing 80 adult female Sprague-Dawley rats (250-300 g), changes in intravesica l pressure and UPP after the intra-arterial and intra-urethral administrati on of phenylephrine, phentolamine, fluoxetine and venlafaxine were monitore d using double-lumen catheters. Results Pretreatment with venlafaxine significantly decreased the contracti on of bladder strips (P=0.01) and significantly increased the contraction o f urethral strips (P = 0.008). In vivo, phenylephrine administered by both routes significantly increased UPP (P = 0.02); phentolamine (arterial) sign ificantly decreased UPP P = 0.001): fluoxetine (arterial) had no effect on UPP. and venlafaxine (both routes) significantly increased UPP (both P<0.00 1). 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 ur inary incontinence, by increasing the UPP.