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Departments of 1Urology and 3Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213; and 2Pharmaceutical Research Division, Takeda Chemical Industries, Osaka 532-8686, Japan
Submitted 5 February 2004 ; accepted in final form 23 April 2004
Urethral closure mechanisms during passive increments in intravesicular pressure (Pves) were investigated using microtip transducer catheters in urethane-anesthetized female rats. After a block of reflex bladder contractions by spinal cord transection at T8-T9, 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 (12.515 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 the iliococcygeous/pubococcygeous muscles, or the hypogastric nerves significantly reduced (4974%) the urethral reflex response induced by passive Pves increases, and combined transection of these three sets of nerves totally abolished the urethra-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, were significantly lowered by 3035% 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 the urethra mediated by activation of sympathetic and somatic nerves and 2) bladder-to-urethral reflexes induced by passive Pves elevation significantly contribute to the prevention of stress urinary incontinence.
stress urinary incontinence; urethral resistance; leak point pressure
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