Lenders Malte, Hofschröer Verena, Schmitz Boris, Kasprzak Bernd, Rohlmann Astrid, Missler Markus, Pavenstädt Hermann, Oberleithner Hans, Brand Stefan-Martin, Kusche-Vihrog Kristina, Brand Eva
aUniversity Hospital Muenster, Internal Medicine D, Nephrology, Hypertension and Rheumatology bUniversity of Muenster, Institute of Physiology II cUniversity Hospital Muenster, Institute of Sports Medicine, Molecular Genetics of Cardiovascular Disease dUniversity Hospital Muenster, Department of Vascular and Endovascular Surgery eUniversity of Muenster, Institute of Anatomy and Molecular Neurobiology, Muenster, Germany *Malte Lenders and Verena Hofschröer contributed equally to the writing of this article. †Kristina Kusche-Vihrog and Eva Brand contributed equally to the writing of this article.
J Hypertens. 2015 Dec;33(12):2455-62. doi: 10.1097/HJH.0000000000000736.
Recently, the nanomechanical properties (i.e. stiffness) of endothelial cells have been identified as crucial for appropriate endothelial function. One major determinant of endothelial stiffness is the endothelial sodium channel (EnNaC). EnNaC-dependent stiffening leads to reduced nitric oxide release, which is a hallmark for endothelial dysfunction. In the current study, we hypothesized that endothelial function is directly linked to the overall function of the arterial system.
Sixty-four human ex-vivo arterial samples were collected from femoral bypass or vein-stripping procedures. Nanomechanical characteristics of ex-vivo endothelium from isolated arterial side branches were determined using atomic force microscopy. The endothelium's potential to respond to EnNaC inhibition by amiloride was defined as endothelial amiloride index. In addition, patients' arterial stiffness was determined by pulse wave velocity (PWV).
Fifty-three percentage of the ex-vivo samples responded 'classically' to amiloride with endothelial softening, whereas 47% of the patients' samples did not. Interestingly, a lack of endothelial softening in the presence of amiloride in vitro was observed with higher frequency among samples obtained from individuals with elevated PWV. Further, an increased PWV was associated with impaired renal function and endothelial dysfunction (higher levels of von Willebrand factor).
Here, we report differential responses of human ex-vivo vessels to amiloride. Although the mechanism of differential amiloride response is still unknown, the data indicate that drug action on endothelial function could differ strongly among patients, especially in those with a vascular end-organ damage determined by PWV.
最近，内皮细胞的纳米力学特性（即硬度）已被确定对适当的内皮功能至关重要。内皮硬度的一个主要决定因素是内皮钠通道（EnNaC）。EnNaC依赖性硬化导致一氧化氮释放减少，这是内皮功能障碍的一个标志。在本研究中，我们假设内皮功能与动脉系统的整体功能直接相关。
从股动脉搭桥或静脉剥脱手术中收集64个人体离体动脉样本。使用原子力显微镜测定离体动脉侧支的离体内皮的纳米力学特性。内皮对氨氯地平抑制EnNaC的反应潜力被定义为内皮氨氯地平指数。此外，通过脉搏波速度（PWV）测定患者的动脉硬度。
53%的离体样本对氨氯地平有“典型”反应，内皮变软，而47%的患者样本没有。有趣的是，在体外存在氨氯地平时缺乏内皮变软的情况在从PWV升高的个体获得的样本中出现的频率更高。此外，PWV升高与肾功能受损和内皮功能障碍（血管性血友病因子水平升高）相关。
在此，我们报告了人体离体血管对氨氯地平的不同反应。尽管氨氯地平反应差异的机制尚不清楚，但数据表明药物对内皮功能的作用在患者之间可能有很大差异，尤其是在那些由PWV确定存在血管终末器官损伤的患者中。
