Activation of the external urethral sphincter central pattern generator by a 5-HT1A receptor agonist in rats with chronic spinal cord injury
Activation of the external urethral sphincter central pattern generator by a 5-HT1A receptor agonist in rats with chronic spinal cord injury
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DOI：
10.1152/ajpregu.00142.2006
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发表时间：
2007-04-01
影响因子：
2.8
通讯作者：
Reiter, Jerome P.
中科院分区：
文献类型：
--
作者：
Dolber, Paul C.;Gu, Baojun;Reiter, Jerome P.
我们最近证明，用 5-HT1A/7 受体激动剂 [(R)-(+)-8-羟基-2-二正丙氨基]四氢萘 (8-OH-DPAT) 治疗可增加氯醛糖麻醉的患有慢性脊髓损伤的雌性猫的膀胱容量。在本研究中，我们研究了 8-OH-DPAT 对患有慢性脊髓损伤（T10 横断）的乌拉坦麻醉雌性大鼠（初始体重 175 - 200 g）的膀胱容量和尿道外括约肌 (EUS) 活动的影响。膀胱测量研究在横切后 8-12 周进行。用经膀胱导管监测尿烷麻醉的大鼠的膀胱内压力，并通过肌电图评估 EUS 活性。脊髓损伤会扰乱 EUS 的阶段性活动，导致排尿效率降低和残余量增加。 8-OH-DPAT 诱导膀胱容量呈剂量依赖性下降（与慢性脊髓损伤猫的效果相反），排尿量增加，排尿效率提高导致残余量减少。排尿效率的意外改善可以通过 8-OH-DPAT 诱导出现阶段性 EUS 松弛来解释。在脊髓完整的大鼠中，8-OH-DPAT 也改变了阶段性 EUS 松弛，而 5-HT1A 受体拮抗剂 N-叔丁基-3-[4-(2-甲氧基苯基)-哌嗪-1-基]-2-苯基丙酰胺 (WAY-100635) 本身没有效果。脊髓损伤后阶段性松弛何时恢复，以及它是否真正丧失或只是暂时与兴奋性输入分离还有待确定。
We recently demonstrated that treatment with the 5-HT1A/7 receptor agonist [(R)-(+)-8-hydroxy-2-di-n-propylamino] tetralin (8-OH-DPAT) increases bladder capacity in chloralose-anesthetized female cats with chronic spinal cord injury. In the current study, we investigated the effects of 8-OH-DPAT on bladder capacity and external urethral sphincter (EUS) activity in urethane-anesthetized female rats (initial body mass 175 - 200 g) with chronic spinal cord injury (transsection at T10). Cystometric study took place 8 - 12 wk posttranssection. Intravesical pressure was monitored in urethane-anesthetized rats with a transvesical catheter, and EUS activity was assessed electromyo-graphically. Spinal cord injury disrupts phasic activity of the EUS, resulting in decreased voiding efficiency and increased residual volume. 8-OH-DPAT induced a dose-dependent decrease in bladder capacity ( the opposite of its effect in chronic spinal cord-injured cats) with an increase in micturition volume and decrease in residual volume resulting from improvement in voiding efficiency. The unexpected improvement in voiding efficiency can be explained by the 8-OH-DPAT induced emergence of phasic EUS relaxation. Phasic EUS relaxation was also altered by 8-OH-DPAT in spinally intact rats, whereas the 5-HT1A receptor antagonist N-tert-butyl-3-[4-(2-methoxyphenyl)-piperazin-1-yl]-2- phenylpropanamide (WAY-100635), on its own, was without effect. It remains to be determined when phasic relaxation is restored after spinal cord injury, and indeed whether it is ever truly lost or is only temporarily separated from excitatory input.