Division of Molecular Pharmacology, Tottori University School of Medicine, Yonago, Japan.
Neurourol Urodyn. 2012 Jun;31(5):695-701. doi: 10.1002/nau.21213. Epub 2012 Mar 30.
There is increasing evidence that ischemia is one of the main etiology in overactive bladder (OAB), and that nicorandil prevents OAB. We investigated the effect of nicorandil on hypertension-related bladder dysfunction in spontaneously hypertensive rats (SHRs).
Twelve-week-old SHRs received six-weeks treatment with nicorandil (0, 3, or 10 mg/kg, i.p. every day). Wistar rats were used for normotensive controls. Six weeks after nicorandil treatment, the bladder blood flow was estimated by hydrogen clearance method, and the bladder functions were estimated by voiding behavior studies and functional studies. Tissue levels of nerve growth factor (NGF) were measured by ELISA method. Furthermore, the participation levels of K(ATP) channel pores were investigated by real-time PCR.
SHRs showed significant increases in blood pressure, micturition frequency, tissue levels of NGF and expressions of both K(IR) 6.1 and K(IR) 6.2 mRNAs, and a significant decrease in the bladder blood flow. The carbachol-induced contractile responses were similar in all groups. Although both doses of nicorandil failed to decrease the blood pressure, nicorandil significantly decreased the micturition frequency, tissue levels of NGF and increased the bladder blood flow in a dose dependent manner. The expressions of K(IR) 6.1 and K(IR) 6.2 mRNAs were slightly up-regulated by the low dose of nicorandil, whereas the high dose of nicorandil significantly up-regulated those expressions compared to non-treated SHRs.
These data indicate that nicorandil prevents hypertension-related bladder dysfunction in the SHR, which may be related to its effect on the increased blood flow in the bladder.
越来越多的证据表明，缺血是膀胱过度活动症（OAB）的主要病因之一，而尼可地尔可预防 OAB。我们研究了尼可地尔对自发性高血压大鼠（SHR）高血压相关膀胱功能障碍的影响。
12 周龄的 SHR 接受尼可地尔（0、3 或 10mg/kg，每天腹腔注射）治疗 6 周。Wistar 大鼠用于正常血压对照。尼可地尔治疗 6 周后，采用氢清除法评估膀胱血流，通过排尿行为研究和功能研究评估膀胱功能。采用 ELISA 法测量神经生长因子（NGF）的组织水平。此外，通过实时 PCR 研究 K(ATP)通道孔的参与水平。
SHR 血压显著升高，排尿频率、组织 NGF 水平和 K(IR) 6.1 和 K(IR) 6.2 mRNA 的表达水平均显著升高，膀胱血流显著减少。各组间卡巴胆碱诱导的收缩反应相似。尽管两种剂量的尼可地尔均未能降低血压，但尼可地尔均能显著降低排尿频率、组织 NGF 水平，并呈剂量依赖性增加膀胱血流。低剂量尼可地尔轻度上调 K(IR) 6.1 和 K(IR) 6.2 mRNA 的表达，而高剂量尼可地尔与未治疗的 SHR 相比，显著上调这些表达。
这些数据表明，尼可地尔可预防 SHR 高血压相关的膀胱功能障碍，这可能与其对膀胱血流增加的作用有关。
