Role of noradrenergic pathways in sneeze-induced urethral continence reflex in rats

Yasuhiro Kaiho, Izumi Kamo, Michael B. Chancellor, Yoichi Arai, William C. De Groat, Naoki Yoshimura

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51 Citations (Scopus)


To clarify the role of noradrenergic pathways in preventing stress urinary incontinence (SUI) during sneezing, we investigated the effect of the norepinephrine reuptake inhibitor nisoxetine and α-adrenoceptor antagonists phentolamine (nonspecific blocker) and prazosin (α 1-receptor-selective blocker) on the neurally evoked urethral continence reflex induced by sneezing in rats. The 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 female adult rats and rats with SUI induced by vaginal distention (VD). In normal rats, intrathecal (it) phentolamine (0.02 nmol) and prazosin (0.02 nmol) decreased A-URS by 11.9 and 15.7%, respectively, without affecting UBP. In both normal and VD rats, intravenous (iv) application of nisoxetine (1 mg/kg) increased A-URS by 17.2 and 18.3% and UBP by 23.7 and 32.7%, respectively. Phentolamine or prazosin (both it) eliminated nisoxetine-induced increases in A-URS, but not the increases in UBP, which were, however, suppressed by iv phentolamine (5 mg/kg) or prazosin (1 mg/kg). Sneezing induced fluid leakage from the urethral orifice in VD rats, but not in normal rats. In VD rats, S-LPP was increased by 30.2% by iv nisoxetine. Application of phentolamine and prazosin (both it) decreased S-LPP by 15.7 and 20.6%, respectively, and nisoxetine induced increases in S-LPP to 13.2 and 12.3%, respectively. These results indicate that activation of the noradrenergic system by a norepinephrine reuptake inhibitor can prevent SUI via α1-adrenoceptors by enhancing the sneeze-induced active urethral closure mechanism at the spinal level and augmenting UBP at the periphery.

Original languageEnglish
Pages (from-to)F639-F646
JournalAmerican Journal of Physiology - Renal Physiology
Issue number2
Publication statusPublished - 2007 Feb


  • Adrenergic reuptake inhibitors
  • Adrenergic α-antagonists
  • Neural pathway
  • Urinary incontinence
  • α-adrenergic receptors

ASJC Scopus subject areas

  • Physiology
  • Urology


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