The Effects of Selective Norepinephrine Reuptake Inhibitors (SNRIs) on the Urethral Pressure

Bae, Jae Hyun; Moon, Du Geon; Lee, Jeong Gu

Abstract

PURPOSE: This study was performed to identify the effects of selective norepinephrine reuptake inhibitor (SNRI, venlafaxine) on the urethral perfusion pressure (UPP) and also to assess its therapeutic potentials for stress urinary incontinence.
MATERIALS AND METHODS
Smooth muscle strips of bladder and proximal urethra were prepared using female New Zealand white rabbits. Each strip was electrically stimulated and the degree of strip contraction was recorded by polygraph. After administration of venlafaxine (10(-6)M), responses of strips to electrical stimulation were measured. In separate experiments of eighty adult female Sprague Dawley rats, intravesical pressure and UPP was measured separately via double lumen catheter. Changes of intravesical pressure and UPP to intra-arterial (i.a.) and intra-urethral (i.u.) administra tion of phenylephrine, phentolamine, nitroprusside, fluoxetine (SSRIs), and venlafaxine were monitored, respectively.
RESULTS
In strip study, pretreatment of venlafaxine significantly decreased the contrac tion of bladder strips (p=0.01) and significantly increased the contraction of urethral strips (p=0.008). In separate experiment of in vivo animal study, phenylephrine signifi cantly increased the UPP. Phentolamine (i.a.) significantly decreased the UPP (p= 0.001). UPP was also significantly decreased by intra urethral infusion of nitroprusside (p=0.003), but not significantly decreased by intra-arterial nitroprusside (p=0.23). Fluoxetine (i.a.) did not increase UPP significantly (p=0.15). Venlafaxine (i.a. and i.u.) significantly increased UPP (p=0.0002, 0.0001), respectively. In each case, intravesical pressure was not changed significantly.
CONCLUSIONS
These results demonstrate that SNRI increases UPP in vitro and in vivo animal study. These results imply that venlafaxine may be useful for treatment of stress urinary incontinence by increasing UPP.