Cardioprotective effect of hydroxyfasudil as a specific Rho-kinase inhibitor, on ischemia-reperfusion injury in canine coronary microvessels in vivo.
Cardioprotective effect of hydroxyfasudil as a specific Rho-kinase inhibitor, on ischemia-reperfusion injury in canine coronary microvessels in vivo.
复制标题
DOI：
--
复制
发表时间：
2006
影响因子：
2.1
通讯作者：
T. Yada;H. Shimokawa;F. Kajiya
中科院分区：
文献类型：
--
作者：
T. Yada;H. Shimokawa;F. Kajiya
Rho激酶调节平滑肌细胞中肌球蛋白轻链的钙敏感性，并被认为在心血管疾病中起致病作用。本研究旨在探讨Rho激酶特异性抑制剂羟基法舒地尔（hydroxyfasudil）对冠状动脉缺血再灌注（I/R）损伤是否具有保护作用，以及NO是否参与其中。应用CCD活体显微镜观察犬冠状动脉I/R时心外膜下小动脉（直径≥ 100 μ m）和小动脉（直径< 100 μ m）的形态学变化。冠状动脉血管反应内皮依赖性（乙酰胆碱）和非依赖性（罂粟碱）血管扩张剂I/R后，在三种条件下进行了检查：控制，预处理，和羟基法舒地尔。冠状动脉I/R显着损害冠状动脉血管舒张乙酰胆碱，而羟基法舒地尔完全保留的反应，预处理。羟基法舒地尔也显著减少心肌梗死面积。上述结果提示，羟基法舒地尔对在体冠状动脉I/R损伤具有保护作用，其机制可能与NO介导有关。
Rho-kinase modulates calcium sensitivity of the myosin light chain in smooth muscle cells and has been implicated as playing a pathogenetic role in cardiovascular disorders. This paper was aimed to determine whether hydroxyfasudil (a specific Rho-kinase inhibitor) exerts cardioprotective effect on coronary ischemia-reperfusion (I/R) injury, and if so, whether NO is involved. Canine subepicardial small arteries (diameter > or = 100 microm) and arterioles (diameter < 100 microm) were observed by a CCD intravital microscope during coronary I/R. Coronary vascular responses to endothelium-dependent (acetylcholine) and -independent (papaverine) vasodilators were examined after I/R under three conditions: control, preconditioning, and hydroxyfasudil. Coronary I/R significantly impaired coronary vasodilation to acetylcholine, whereas hydroxyfasudil completely preserved the responses, as did preconditioning. Hydroxyfasudil also significantly reduced myocardial infarct size. These results indicated that hydroxyfasudil exerts cardioprotective effects on coronary I/R injury in vivo, for which NO-mediated mechanism may be involved.