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.


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 micromol/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.
Bae
J H
JH
Department of Urology, Korea University College of Medicine, Seoul.
Moon
D G
DG
Lee
J G
JG
D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003511:Cyclohexanols / Q000494:pharmacology* / Q000627:therapeutic use; D004558:Electric Stimulation; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects; D011312:Pressure; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014521:Urethra / Q000187:drug effects* / Q000502:physiology; D014550:Urinary Incontinence, Stress / Q000188:drug therapy* / Q000503:physiopathology; D000069470:Venlafaxine Hydrochloride
D018759:Adrenergic Uptake Inhibitors; D003511:Cyclohexanols; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride