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1 Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA; Pharmaceutical Research Division, Takeda Chemical Industries Ltd, Osaka, Osaka, Japan
2 Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA
3 Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA, USA
4 Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA, USA
* To whom correspondence should be addressed. E-mail: nyos{at}pitt.edu.
Urethral closure mechanisms during passive increments in intravesical pressure (Pves) were investigated using microtip transducer catheters in urethane-anesthetized female rats. Following block of reflex bladder contractions by spinal cord transection at Th8-9, abruptly raising Pves to 20, 40 or 60 cmH2O for 2 min induced a bladder pressure-dependent contractile response in a restricted portion of the middle urethra (12.5-15 mm from the urethral orifice) that was abolished by cutting the pelvic nerves bilaterally. In pelvic nerve-intact rats, the bilateral transection of either the pudendal nerves, the nerves to iliococcygeous/pubococcygeous muscles or the hypogastric nerves significantly reduced (49%-74%) the urethral reflex response induced by passive Pves increases, and combined transection of these three sets of nerves totally abolished the urethral closing responses. In spinal cord-intact rats, similar urethral contractile responses were elicited during Pves elevation (20 or 40 cmH2O) and were also eliminated by bilateral pelvic nerve transection. After spinal cord and pelvic nerve transection, leak point pressures, defined as the pressure inducing fluid leakage from the urethral orifice during passive Pves elevation by either bladder pressure clamping in 2.5 cmH2O steps or direct compression of the bladder was significantly lowered by 30%-35% compared with sham-operated (spinal cord-transected and pelvic nerve-intact) rats. These results indicate that: (1) passive elevation of Pves can elicit pelvic afferent nerve-mediated contractile reflexes in the restricted portion of urethra mediated by activation of sympathetic and somatic nerves, (2) bladder-to-urethral reflexes induced by passive Pves elevation significantly contribute to the prevention of SUI.
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