title: Effects of Duloxetine on Urethral Continence Reflex and Bladder Activity in Rats with Cerebral Infarction.
abstract: OBJECTIVE
  We investigated the effect of duloxetine, a norepinephrine and serotonin reuptake inhibitor, on the sneeze induced continence reflex and on bladder function in rats with cerebral infarction.
  
  
  METHODS
  Using urethane anesthesia the effect of duloxetine (1 mg/kg intravenously) on the amplitude of urethral responses during sneezing as well as urethral baseline pressure at the mid urethra was evaluated in normal female adult rats and cerebral infarction rats. Tilt leak point pressure was also measured. In normal and cerebral infarction rats continuous cystometry was evaluated before and after duloxetine injection.
  
  
  RESULTS
  In cerebral infarction rats urethral baseline pressure was 43% lower than in normal rats but the amplitude of urethral responses during sneezing did not differ in the 2 groups. Duloxetine increased the amplitude of urethral responses during sneezing and urethral baseline pressure by 31% and 21%, respectively, in normal rats but did not affect either in cerebral infarction rats. Also, in cerebral infarction rats leak point pressure was 29% lower compared with normal rats. Duloxetine increased leak point pressure in normal rats but not in cerebral infarction rats. Cerebral infarction reduced intercontraction intervals without affecting the amplitude of bladder contractions compared with normal rats. Duloxetine prolonged intercontraction intervals in cerebral infarction rats but not in normal rats.
  
  
  CONCLUSIONS
  These results suggest that cerebral infarction induces not only bladder overactivity but also stress urinary incontinence, which may account for mixed incontinence in patients with cerebral infarction. After cerebral infarction duloxetine reduced bladder overactivity but failed to enhance active urethral closure mechanisms during sneezing, suggesting that disorganization of the brain network after cerebral infarction might influence the effect of duloxetine on lower urinary tract function.
authors: Department of Urology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan; Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Electronic address: miyaz929@med.u-ryukyu.ac.jp.
authors: Minoru
authors: M
authors: Miyazato
authors: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors: Takeya
authors: T
authors: Kitta
authors: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors: Yasuhiro
authors: Y
authors: Kaiho
authors: Department of Urology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors: Takuma
authors: T
authors: Oshiro
authors: Department of Urology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors: Seiichi
authors: S
authors: Saito
authors: Department of Urology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan.
authors: Michael B
authors: MB
authors: Chancellor
authors: Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors: William C
authors: WC
authors: de Groat
authors: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors: Naoki
authors: N
authors: Yoshimura
mesh_terms: D000818:Animals; D002544:Cerebral Infarction / Q000503:physiopathology*; D000068736:Duloxetine Hydrochloride; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012912:Sneezing; D013876:Thiophenes / Q000494:pharmacology*; D014521:Urethra / Q000187:drug effects* / Q000503:physiopathology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology*; D014554:Urination
chemical_list: D000068736:Duloxetine Hydrochloride; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes
keywords: cerebral infarction; duloxetine; stress; urethra; urinary bladder; urinary incontinence