Southern Knights' Laboratory LLP, Okinawa, Japan; Department of Urology, Okinawa Kyodo Hospital, Okinawa, Japan.
Life Sci. 2013 May 30;92(20-21):1024-8. doi: 10.1016/j.lfs.2013.03.021. Epub 2013 Apr 10.
Alpha1D-adrenoceptors (α1D-ARs) located in the spinal cord are involved in the control of lower urinary tract function. In order to clarify the effect of α1D-ARs on storage function in the spinal cord, we examined the effect of oral administration and intrathecal injection of the α1D/A-AR antagonist, naftopidil, on bladder activity, as well as the effect of naftopidil on bladder wall histology, in female rats with spinal cord injury (SCI).
Adult female Sprague-Dawley rats with Th9-10 spinal cord transection were used. In SCI rats with or without 5mg/day of naftopidil for 4weeks, bladder activity was examined via continuous cystometry. In other SCI rats, bladder activity was examined before and after intrathecal injection of naftopidil. In addition, bladder wall histology was compared between SCI rats with or without oral administration of naftopidil for 4weeks.
Oral administration of naftopidil decreased the number of non-voiding contractions (NVCs). Intrathecal injection of naftopidil prolonged the interval between voiding contractions, decreased the maximum voiding contraction pressure and the number of NVCs, and increased bladder capacity without affecting the residual urine volume. Oral administration of naftopidil also decreased bladder wall fibrosis.
The α1D/A-AR antagonist naftopidil might act on the bladder and spinal cord to improve detrusor hyperreflexia in the storage state in SCI female rats. Naftopidil also suppressed bladder wall fibrosis, suggesting that it may be effective for the treatment of neurogenic lower urinary tract dysfunction after SCI.
位于脊髓的α1D-肾上腺素能受体（α1D-ARs）参与下尿路功能的控制。为了阐明α1D-ARs 对脊髓储存功能的影响，我们研究了口服和鞘内注射α1D/A-AR 拮抗剂萘哌地尔对脊髓损伤（SCI）雌性大鼠膀胱活动的影响，以及萘哌地尔对膀胱壁组织学的影响。
使用成年雌性 Sprague-Dawley 大鼠，行 Th9-10 脊髓横断。在 SCI 大鼠中，给予或不给予 5mg/天萘哌地尔治疗 4 周，通过连续膀胱测压检查膀胱活动。在其他 SCI 大鼠中，在鞘内注射萘哌地尔前后检查膀胱活动。此外，比较了口服萘哌地尔治疗 4 周的 SCI 大鼠和未治疗的 SCI 大鼠的膀胱壁组织学。
口服萘哌地尔减少了非排尿收缩（NVCs）的次数。鞘内注射萘哌地尔延长了排尿收缩之间的间隔，降低了最大排尿收缩压和 NVCs 的次数，并增加了膀胱容量，而不影响残余尿量。口服萘哌地尔也减少了膀胱壁纤维化。
α1D/A-AR 拮抗剂萘哌地尔可能通过作用于膀胱和脊髓来改善 SCI 雌性大鼠储存状态下的逼尿肌反射亢进。萘哌地尔还抑制了膀胱壁纤维化，表明它可能对 SCI 后神经源性下尿路功能障碍的治疗有效。
