Department of Molecular and Cellular Sport Medicine, Institute for Circulation Research and Sport Medicine, German Sports University Cologne, Cologne, Germany.
Phytomedicine. 2011 Dec 15;19(1):20-4. doi: 10.1016/j.phymed.2011.08.059. Epub 2011 Sep 6.
WS(®) 1442 is a special extract of hawthorn leaves with flowers used for the treatment of mild cardiac failure. The activation of endothelial nitric oxide synthase (eNOS) has been shown to contribute to its vasodilating properties. Quite recently it has been demonstrated that red blood cells (RBCs) express a functional NO-synthase (rbcNOS) and rbcNOS activation has been associated with increased RBC deformability. The aim of the present study was to determine whether WS(®) 1442 is able to activate rbcNOS, to induce NO-formation in RBC and to alter RBC-deformability. Blood from healthy volunteers was incubated with WS(®) 1442 (25-100 μg/ml) for up to 30 min. RbcNOS activation was detected by immunohistochemical staining of phosphorylated rbcNOS and NO-formation was examined by diaminofluorescein (DAF) fluorescence. RBC deformability was measured by a laser assisted optical rotational cell analyzer. Serine 1177 of RbcNOS (rbcNOS Ser(1177)) was time- and concentration-dependently phosphorylated by WS(®) 1442. Rates of rbcNOS Ser(1177) phosphorylation were up to 149% higher in RBCs treated with WS(®) 1442 in comparison to control (DMSO 0.05%). WS(®) 1442 induced a time-dependent increase in NO-formation in RBCs which reached its maximum after 5 min. An increase in shear stress (0.3-50 Pa) caused an increase in RBC deformability. WS(®) 1442 did not change either basal or maximal RBC-deformability or shear stress sensitivity of RBC at normoxia.
WS(®) 1442 activates rbcNOS and causes NO-formation in RBCs. WS(®) 1442-dependent NO-formation however does not affect RBC-deformability at normoxia.
WS(®) 1442 是山楂叶和花的特殊提取物，用于治疗轻度心力衰竭。现已证实，内皮型一氧化氮合酶（eNOS）的激活有助于其血管舒张特性。最近有研究表明，红细胞（RBC）表达一种功能性一氧化氮合酶（rbcNOS），rbcNOS 的激活与 RBC 变形能力的增加有关。本研究旨在确定 WS(®) 1442 是否能够激活 rbcNOS，在 RBC 中诱导 NO 的形成，并改变 RBC 的变形能力。将健康志愿者的血液与 WS(®) 1442（25-100 μg/ml）孵育长达 30 分钟。通过磷酸化 rbcNOS 的免疫组织化学染色检测 rbcNOS 的激活，通过二氨基荧光素（DAF）荧光检测 NO 的形成。通过激光辅助光学旋转细胞分析仪测量 RBC 的变形能力。WS(®) 1442 可使 rbcNOS 的丝氨酸 1177（rbcNOS Ser(1177)）时间和浓度依赖性磷酸化。与对照（DMSO 0.05%）相比，用 WS(®) 1442 处理的 RBC 中 rbcNOS Ser(1177)的磷酸化速率高达 149%。WS(®) 1442 可诱导 RBC 中 NO 的形成呈时间依赖性增加，5 分钟后达到最大值。剪切应力（0.3-50 Pa）的增加会导致 RBC 变形能力增加。WS(®) 1442 在常氧条件下不会改变 RBC 的基础或最大变形能力或 RBC 对剪切应力的敏感性。
WS(®) 1442 激活 rbcNOS 并在 RBC 中引起 NO 的形成。然而，WS(®) 1442 依赖性的 NO 形成不会影响常氧下 RBC 的变形能力。
