Improvement in bladder storage function by tamsulosin depends on suppression of C-fiber urethral afferent activity in rats
Improvement in bladder storage function by tamsulosin depends on suppression of C-fiber urethral afferent activity in rats
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DOI：
10.1016/j.juro.2006.09.076
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发表时间：
2007-02-01
影响因子：
6.6
通讯作者：
Akino, Hironobu
中科院分区：
文献类型：
--
作者：
Yokoyama, Osamu;Yusup, Anwar;Akino, Hironobu
目的：α(1)受体阻滞剂通过降低前列腺和尿道的肌张力来改善排尿症状。然而，据我们所知，储存症状改善的潜在机制尚不清楚。大鼠下尿路局部应用前列腺素E可刺激排尿反射。采用动物模型，研究α(1)受体阻断剂坦索罗辛(日本东京Astellas Pharma)是否对C纤维传入活动产生影响，如果是，则确定这种作用的部位。材料和方法：在实验前2天，皮下注射0.3 mg/kg树脂毒素，以诱导C纤维传入活动脱敏。乌拉坦麻醉下同步记录大鼠尿路压力和节律性膀胱压力。用前列腺素E-2(0.4 mg/ml)连续灌胃或输尿管给药。结果：前列腺素E-2膀胱内或尿路内给药后，大鼠膀胱收缩间期明显缩短，而白藜芦醇大鼠则无明显变化。这一作用可被EP1受体拮抗剂ONO-8711(6-[(2S，3S)-3-(4-chloro-2-methylphenylsulfonylaminomethyl)-bicyclo[2.2.2]octan-2-yl]5Z-hexenoic酸所拮抗。静脉注射坦索罗辛可显著延长前列腺素E_2所致非瑞尼罗毒素大鼠的膀胱收缩间期，但对前列腺素E_2膀胱内注射的非瑞尼菲大鼠无明显影响。鞘内注射坦索罗辛后，前列腺素E-2可使非瑞尼菲毒素大鼠的膀胱收缩间期略有延长，但差异不显著。结论：前列腺素E-2可通过C纤维传入增强排尿反射，坦索罗辛对C纤维传入神经有抑制作用，从而改善膀胱储存功能。
Purpose: alpha(1)-Blockers improve voiding symptoms by decreasing prostatic and urethral smooth muscle tone. However, to our knowledge the mechanism underlying improvements in storage symptoms is not known. Topical application of prostaglandin E, to the rat lower urinary tract stimulates the micturition reflex. Using an animal model we investigated whether the alpha(1)-blocker tamsulosin (Astellas Pharma, Tokyo, Japan) acts on C-fiber afferent activity and, if so, the location of this effect.Materials and Methods: To induce desensitization of C-fiber afferent activity resiniferatoxin (0.3 mg/kg) was subcutaneously injected in female Sprague-Dawley rats 2 days before experiments. Simultaneous recordings of urethral pressure and rhythmic bladder pressure were made with the rats under urethane anesthesia. Prostaglandin E-2 (0.4 mg/ml) was continuously administered intravesically or intraurethrally to rats pretreated with resiniferatoxin (resiniferatoxin rats) or rats without pretreatment (nonresiniferatoxin rats). We investigated the effects on the micturition reflex of intravenous (2.2 x 10(-1) to 2.2 x 10(3) nM/kg) or intrathecal (0.001 to 0.1 nmol) administration of tamsulosin.Results: The bladder contraction interval was markedly decreased after intravesical or intraurethral administration of prostaglandin E-2 in nonresiniferatoxin rats but it was unchanged in resiniferatoxin rats. This effect was antagonized by the EP1 receptor antagonist ONO-8711 (6-[(2S,3S)-3-(4-chloro-2-methylphenylsulfonylaminomethyl)-bicyclo[2.2.2]octan-2-yl]5Z-hexenoic acid). Intravenous administration of tamsulosin significantly increased the bladder contraction interval in nonresiniferatoxin rats receiving intraurethral prostaglandin E2 but it had no effect on nonresiniferatoxin rats receiving intravesical prostaglandin E,. Intrathecal administration of tamsulosin produced a slight and insignificant increase in the bladder contraction interval in nonresiniferatoxin rats receiving intraurethral prostaglandin E-2.Conclusions: These results suggest that prostaglandin E-2 enhances the micturition reflex through C-fiber afferents and tamsulosin had an inhibitory effect on the C-fiber urethral afferent nerves, thereby improving bladder storage function.