Effect of duloxetine, a norepinephrine and serotonin reuptake inhibitor, on sneeze-induced urethral continence reflex in rats

Minoru Miyazato, Yasuhiro Kaiho, Izumi Kamo, Michael B. Chancellor, Kimio Sugaya, William C. De Groat, Naoki Yoshimura

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

We investigated the effect of duloxetine, a norepinephrine (NE) and serotonin (5-HT) reuptake inhibitor, on the neurally evoked urethral continence reflex induced by sneezing in rats. To clarify the role of noradrenergic and serotonergic mechanisms in preventing stress urinary incontinence (SUI) during sneezing, we examined the effect of duloxetine followed by intrathecal (it) methiothepin maleate (5-HT receptor and α1-adrenoceptor antagonist) or terazosin or idazoxan (selective α1- and α2-adrenoceptor antagonists, respectively). Amplitude of urethral pressure responses during sneezing (A-URS), urethral baseline pressure (UBP) at the midurethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal adult female rats and rats with SUI induced by vaginal distension (VD). In normal and VD rats, intravenous application of duloxetine (1 mg/kg) increased AURS by 35% and 34% and UBP by 21% and 34%, respectively. Sneezing-induced fluid leakage from the urethral orifice was observed in VD rats but not in normal rats. S-LPP was increased from 39.1 to 92.2 cmH2O by intravenous duloxetine in incontinent VD rats. Duloxetine-mediated enhancement of A-URS was inhibited by terazosin but not methiothepin maleate (it). In addition, simultaneous intrathecal application of methiothepin and terazosin induced a reduction in A-URS during sneezing, which was not increased by intravenous duloxetine. However, the reduced A-URS after intrathecal application of methiothepin and terazosin returned to the control level when duloxetine (iv) was applied after intrathecal idazoxan administration. These results indicate that duloxetine can prevent SUI by facilitating noradrenergic and serotonergic systems in the spinal cord to enhance the sneeze-induced active urethral closure mechanism.

Original languageEnglish
Pages (from-to)F264-F271
JournalAmerican Journal of Physiology - Renal Physiology
Volume295
Issue number1
DOIs
Publication statusPublished - 2008 Jul

Keywords

  • Adrenergic and serotonergic reuptake inhibitors
  • Birth trauma
  • Neural pathway
  • Urinary incontinence

ASJC Scopus subject areas

  • Physiology
  • Urology

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