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Sex differences in neonatal rat bladder and external urethral sphincter function caused by bladder reduction
Oreoluwa Ogunyemi, MD, China Chien, BA, Hsi-Yang Wu, MD.
Stanford University, Stanford, CA, USA.

BACKGROUND: Early in life bladder inflammation lowers the threshold for bladder pain in adult rats, but surgical bladder reduction (BR) at 1 week of life increases adult bladder capacity. Serotonergic agonists are known to improve bladder emptying in adult rats by enhancing external urethral sphincter (EUS) function. Since it is unclear why 2 models of increased bladder afferent sensation would lead to opposing effects, we proposed to study the bladder and EUS changes caused by BR, and determine the role that serotonin plays in these responses.
METHODS: 46 Sprague-Dawley rats underwent BR and 52 underwent sham surgery at one week of age. At 3, 6, and 9 weeks, all animals underwent cystometry to evaluate bladder and EUS function. 8-OH-DPAT (serotonergic receptor agonist) and WAY 100,635 (serotonergic receptor antagonist) were administered intravenously. 15 to 16 animals were analyzed at each time point. Bladder parameters included voiding threshold (VT), pressure threshold (PT), maximal intravesical pressure (IVP), and contraction duration. EUS parameters included burst amplitude, burst duration, contraction area under the curve (AUC) and storage tonic AUC. Results were analyzed using Student’s t test.
RESULTS: BR caused an increase in VT in 9 week old female rats (BR 0.81 mL vs. sham 0.36 mL, p<0.05) but did not change VT in male rats. 3 week BR females had a higher PT (BR: 31.1 cm H20 vs. sham: 22.7 cm H20, p<0.01), but no difference was seen in male rats. BR caused a significant decrease in burst amplitude at 3 weeks in both males (BR: 0.17 mV vs. sham 0.28 mV, p<0.05) and females (BR 0.04 mV vs. sham 0.07 mV, p<0.05) but no difference at 6 and 9 weeks. In BR females, 8-OH-DPAT increased storage tonic AUC and burst duration, as it did in control animals. In BR males, 8-OH-DPAT increased EUS burst amplitude and duration, and decreased IVP, similar to control animals.
CONCLUSIONS: BR causes a short term impairment in EUS emptying at 3 weeks of life in both male and female rats, but a long term response is only seen in adult females, who have an increased VT. This change suggests that BR alters the normal maturation of voiding by raising afferent thresholds to result in a larger bladder capacity. BR probably does not act by a serotonergic mechanism, since serotonergic agonists caused similar effects in both sham and BR animals. Changes in bladder afferent sensation and EUS function are more likely to cause abnormal function in females.

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