Dolber Paul C, Gu Baojun, Zhang Xiaoyang, Fraser Matthew O, Thor Karl B, Reiter Jerome P
Department of Surgery, Veterans Affairs Medical Center, Durham, NC, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Apr;292(4):R1699-706. doi: 10.1152/ajpregu.00142.2006. Epub 2007 Jan 4.
We recently demonstrated that treatment with the 5-HT(1A/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 electromyographically. 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-HT(1A) 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.
我们最近证明，用5-羟色胺（1A/7）受体激动剂[（R）-（+）-8-羟基-2-二正丙基氨基]四氢萘（8-OH-DPAT）进行治疗，可增加慢性脊髓损伤的水合氯醛麻醉雌性猫的膀胱容量。在当前研究中，我们调查了8-OH-DPAT对慢性脊髓损伤（T10横断）的氨基甲酸乙酯麻醉雌性大鼠（初始体重175 - 200克）膀胱容量和尿道外括约肌（EUS）活动的影响。在横断后8 - 12周进行膀胱测压研究。用经膀胱导管监测氨基甲酸乙酯麻醉大鼠的膀胱内压，并通过肌电图评估EUS活动。脊髓损伤会破坏EUS的阶段性活动，导致排尿效率降低和残余尿量增加。8-OH-DPAT导致膀胱容量呈剂量依赖性降低（与其对慢性脊髓损伤猫的作用相反），排尿量增加，残余尿量减少，这是由于排尿效率提高所致。排尿效率的意外改善可以用8-OH-DPAT诱导的EUS阶段性松弛来解释。在脊髓完整的大鼠中，8-OH-DPAT也改变了EUS的阶段性松弛，而5-羟色胺（1A）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）单独使用时没有效果。脊髓损伤后阶段性松弛何时恢复，以及它是否真的丧失或只是暂时与兴奋性输入分离，仍有待确定。
