Involvement of reflex urethral closure mechanisms in urethral resistance under momentary stress condition induced by electrical stimulation of rat abdomen.
A novel method for evaluating the urethral resistance during abrupt elevation of abdominal pressure was developed in spinalized female rats under urethane anesthesia. Electrical stimulation of abdominal muscles for 1 s induced increases in both the intra-abdominal and the intravesical pressure in a stimulus-dependent manner, and the bladder response was almost lost when the abdomen was opened. The lowest intravesical pressure during electrical stimulation that induced fluid leakage from the urethral orifice (leak point pressure) and the maximal intravesical pressure without urine leakage below the leak point pressure were evaluated as the indexes of urethral resistance. Lower urethral resistance was obtained in the rats whose pelvic nerves or somatic nerves containing pudendal nerves and nerves to iliococcygeus/pubococcygeus muscles were transected bilaterally. In contrast, transection of bilateral hypogastric nerves showed smaller effects. Duloxetine, a drug for stress urinary incontinence, enlarged the reflex urethral closing contractions that were induced by an increase in intravesical pressure and measured using a microtip transducer catheter in the middle urethra. This drug also increased the urethral resistance (leak point pressure), whereas it did not show any effect in the rats whose pelvic nerves were bilaterally transected, showing that the augmentation of the reflex urethral closure by the drug resulted in the elevation of the urethral resistance. From these findings, it was concluded that during momentary elevation of abdominal pressure, the reflex urethral closure mechanisms via bladder-spinal cord-urethral sphincter and pelvic floor muscles greatly contribute to the increase in the urethral resistance to prevent the urinary incontinence.
Kamo
Izumi
I
Pharmaceutical Research Division, Takeda Pharmaceutical Company, Limited, 17-85 Jusohonmachi 2-chome, Yodogawa-ku, Osaka 532-8686, Japan. kamo_izumi@takeda.co.jp
Hashimoto
Tadatoshi
T
D000005:Abdomen / Q000294:innervation / Q000502:physiology*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000068736:Duloxetine Hydrochloride; D004558:Electric Stimulation; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology*; D013876:Thiophenes / Q000494:pharmacology; D014521:Urethra / Q000187:drug effects / Q000502:physiology*
D018759:Adrenergic Uptake Inhibitors; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride