Effects of tolterodine on an overactive bladder depend on suppression of C-fiber bladder afferent activity in rats
Effects of tolterodine on an overactive bladder depend on suppression of C-fiber bladder afferent activity in rats
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DOI：
10.1097/01.ju.0000176793.50410.9e
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发表时间：
2005-11-01
影响因子：
6.6
通讯作者：
Akino, H
中科院分区：
文献类型：
--
作者：
Yokoyama, O;Yusup, A;Akino, H
目的：我们确定抗毒蕈碱药的作用是否取决于 C 纤维膀胱传入神经的抑制。我们静脉内或膀胱内给予托特罗定。 材料和方法：为了诱导 C 纤维膀胱传入神经脱敏，在左侧大脑中动脉闭塞 (MCAO) 前 2 天，向雌性 Sprague-Dawley 大鼠皮下注射树脂毒素 (RTX) (0.3 mg/kg)。作为对照，我们使用用乙醇和盐水载体（VEH）治疗的大鼠。通过膀胱穹顶插入聚乙烯导管并使用氟烷麻醉进行 MCAO。在患有脑梗塞 (CI) 的清醒大鼠中研究了静脉注射（0.2 至 2000 nM/kg）或膀胱注射（0.2 或 2 nM）托特罗定（一种抗毒蕈碱剂）对膀胱内压造影的影响。托特罗定膀胱内滴注30分钟，并重复膀胱测压。结果：RTX治疗(RTX-CI)和VEH治疗(VEH-CI)大鼠MCAO后膀胱容量(BC)显着下降。低托特罗定剂量（0.2 或 2 nM/kg）显着增加 VEH-CI 大鼠的 BC，而不增加残余体积，但对 RTX-CI 大鼠的 BC 没有影响。在最高剂量（2,000 nM/kg）下，该药物显着降低了 RTX-CI 和 VEH-CI 大鼠的膀胱收缩压力并增加了残余容量。膀胱内给予托特罗定（0.2 或 2 nM）可显着增加 VEH-CI 大鼠的 BC。然而，托特罗定对 RTX-CI 大鼠的 BC 没有影响。结论：这些结果表明，低剂量托特罗定对 C 纤维膀胱传入神经产生抑制作用，从而改善储存期的 BC。
Purpose: We determined whether the effects of antimuscarinics depend on the suppression of C-fiber bladder afferent nerves. We administered tolterodine intravenously or intravesically.Materials and Methods: To induce C-fiber bladder afferent nerve desensitization resiniferatoxin (RTX) (0.3 mg/kg) was injected subcutaneously in female Sprague-Dawley rats 2 days prior to left middle cerebral artery occlusion (MCAO). As controls, we used rats treated with ethanol and saline vehicle (VEH). Insertion of a polyethylene catheter through the bladder dome and MCAO were performed using halothane anesthesia. The effects of intravenous (0.2 to 2000 nM/kg) or intravesical (0.2 or 2 nM) tolterodine, an antimuscarinic agent, on cystometrography were investigated in conscious rats with a cerebral infarct (CI). Tolterodine was instilled intravesically for 30 minutes and cystometry was repeated.Results: Bladder capacity (BC) was markedly decreased after MCAO in RTX treated (RTX-CI) and VEH treated (VEH-CI) rats. Low tolterodine doses (0.2 or 2 nM/kg) significantly increased BC in VEH-CI rats without increasing residual volume but it had no effects on BC in RTX-CI rats. At the highest dose (2,000 nM/kg) the drug significantly decreased bladder contraction pressure and increased residual volume in RTX-CI and VEH-CI rats. Intravesical administration of tolterodine (0.2 or 2 nM) significantly increased BC in VEH-CI rats. However, tolterodine had no effect on BC in RTX-CI rats.Conclusions: These results suggest that at low doses tolterodine exerts an inhibitory effect on C-fiber bladder afferent nerves, thereby, improving BC during the storage phase.