Christ George J, Andersson Karl-Erik
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Neurourol Urodyn. 2007 Oct;26(6 Suppl):948-54. doi: 10.1002/nau.20475.
Altered smooth muscle cell contractility/tone contributes, at least in part, to the lower urinary tract symptoms (LUTS) seen in men with benign prostatic obstruction (BPO). Accordingly, many of the therapies to date have focused largely on blockade of individual membrane receptors to diminish smooth muscle contractility and provide symptomatic relief. This pharmacologic approach has been associated with variable results, limited efficacy, and untoward side effects. Such limited clinical success is not surprising given the plethora of neurotransmitters, neuromodulators, and hormones that are now known to modulate LUT smooth muscle cell tone. In the pursuit of improved treatment options, more recent investigations have focused attention on intracellular signal transduction events that represent convergence points for membrane receptor activation. In particular, calcium sensitization and the role of the Rho-kinase pathway has received much attention. In this report, we review the literature on the role of the Rho-kinase pathway in the modulation of LUT smooth muscle cell tone. In short, the available data support an important role for Rho-kinase in the physiologic and pathophysiologic regulation of LUT smooth muscle cell tone. Rho-kinase inhibitors thus appear to represent a potentially attractive therapeutic possibility for the treatment of LUTS.
平滑肌细胞收缩性/张力改变至少在一定程度上导致了良性前列腺梗阻（BPO）男性出现下尿路症状（LUTS）。因此，迄今为止的许多治疗方法主要集中在阻断单个膜受体以减少平滑肌收缩性并提供症状缓解。这种药理学方法已产生了不同的结果、疗效有限且有不良副作用。鉴于目前已知有大量神经递质、神经调节剂和激素可调节下尿路平滑肌细胞张力，这样有限的临床成功并不令人惊讶。为了寻求更好的治疗选择，最近的研究将注意力集中在代表膜受体激活汇聚点的细胞内信号转导事件上。特别是，钙敏化和Rho激酶途径的作用受到了很多关注。在本报告中，我们综述了关于Rho激酶途径在调节下尿路平滑肌细胞张力中作用的文献。简而言之，现有数据支持Rho激酶在下尿路平滑肌细胞张力的生理和病理生理调节中起重要作用。因此，Rho激酶抑制剂似乎代表了一种治疗LUTS的潜在有吸引力的治疗可能性。
