Effect of Rho Kinase Inhibitor Ripasudil (K-115) on Isolated Porcine Retinal Arterioles
Effect of Rho Kinase Inhibitor Ripasudil (K-115) on Isolated Porcine Retinal Arterioles
复制标题
Rho 激酶抑制剂利帕舒地尔 (K-115) 对离体猪视网膜小动脉的影响
DOI：
10.1089/jop.2020.0082
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发表时间：
2021
影响因子：
2.3
通讯作者：
Yoshida Akitoshi
中科院分区：
文献类型：
--
作者：
Kamiya Takayuki;Omae Tsuneaki;Nakabayashi Seigo;Takahashi Kengo;Tanner Akira;Yoshida Akitoshi
目的：研究新型Rho相关螺旋线圈蛋白激酶(ROCK)抑制剂雷帕舒地尔(K-115)对视网膜小动脉的松弛作用。我们确定雷帕舒地尔对视网膜微血管管径的作用是否依赖于血管内皮细胞和/或血管中的钾通道，目的是揭示这种血管运动活动所需的信号机制，并抑制内皮素-1(ET-1)的作用。方法：在这项体外研究中，我们分离了猪视网膜小动脉，这些小动脉被插管并加压，没有血流。结果：以剂量依赖的方式(10 NM-30 μM)，视网膜小动脉松弛[最大静息直径%，160.3% ± 7.7%(平均 ± 标准误差)]。非选择性钾通道阻滞剂四乙铵、钙激活的大电导钾通道阻滞剂伊比略毒素、电压门控性钾通道阻滞剂4-AP、ATP敏感性钾通道阻滞剂格列本脲和内向整流钾通道阻滞剂BaCl2对雷帕舒地尔的血管松弛作用无影响。Ripasudil对ET-1引起的视网膜小动脉的血管收缩有相似程度的抑制作用。结论：ROCK抑制剂Ripasudil可引起内皮非依赖性的松弛，并抑制ET-1对视网膜小动脉的作用。确定雷帕舒地尔对视网膜微血管的松弛特性将可能支持青光眼潜在治疗方法的开发。
Purpose:To investigate the vasorelaxation effect of ripasudil (K-115), a novel Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, on isolated retinal arterioles. We determined whether the actions of ripasudil on the retinal microvascular diameter were dependent on the endothelium and/or potassium channels in the smooth muscle, with the goals of uncovering the signaling mechanisms required for this vasomotor activity and inhibiting the action of endothelin-1 (ET-1).Methods:In thisin vitrostudy, we isolated porcine retinal arterioles, which were cannulated and pressurized without flow. We recorded diametric changes using videomicroscopic techniques.Results:In a dose-dependent (10 nM–30 μM) manner, retinal arterioles were relaxed in response to ripasudil [maximum % resting diameter, 160.3% ± 7.7% (mean ± standard error of the mean)]. The ripasudil-induced vasorelaxation was unaffected by endothelium removal, using nonselective potassium channel blocker tetraethylammonium, Ca2+-activated large-conductance potassium channel blocker iberiotoxin, voltage-gated potassium channel blocker 4-AP, ATP-sensitive potassium channel blocker glibenclamide, and inward rectifier potassium channel blocker BaCl2. Ripasudil prevented ET-1-caused vasoconstriction of the retinal arterioles regardless of the presence of endothelium to a similar extent.Conclusion:The ROCK inhibitor ripasudil elicits endothelium-independent relaxation and inhibits the action of ET-1 on the retinal arterioles. Determining the relaxation properties of ripasudil on the retinal microvasculature will likely support the development of potential therapies for glaucoma.