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Am J Physiol Renal Physiol 292: F639-F646, 2007. First published October 17, 2006; doi:10.1152/ajprenal.00226.2006
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Role of noradrenergic pathways in sneeze-induced urethral continence reflex in rats

Departments of ¹Urology and ³Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and ²Department of Urology, Tohoku University School of Medicine, Sendai, Japan

Submitted 19 June 2006 ; accepted in final form 14 October 2006

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 -adrenoceptor antagonists phentolamine (nonspecific blocker) and prazosin (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 _1-adrenoceptors by enhancing the sneeze-induced active urethral closure mechanism at the spinal level and augmenting UBP at the periphery.

urinary incontinence; neural pathway; adrenergic reuptake inhibitors; adrenergic -antagonists; -adrenergic receptors

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				M. Miyazato, Y. Kaiho, I. Kamo, M. B. Chancellor, K. Sugaya, W. C. de Groat, and N. Yoshimura Effect of duloxetine, a norepinephrine and serotonin reuptake inhibitor, on sneeze-induced urethral continence reflex in rats Am J Physiol Renal Physiol, July 1, 2008; 295(1): F264 - F271. [Abstract] [Full Text] [PDF]

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