Brixius Klara, Willms Sonja, Napp Andreas, Tossios Paschalios, Ladage Dennis, Bloch Wilhelm, Mehlhorn Uwe, Schwinger Robert H G
Laboratory of Muscle Research and Molecular Cardiology, Clinic III for Internal Medicine, University of Cologne, Joseph-Stelzmann-Str. 9, D-50924, Cologne, Germany, Robert.
Cardiovasc Drugs Ther. 2006 Jun;20(3):177-84. doi: 10.1007/s10557-006-8723-7.
This study investigates the influence of WS(R) 1442, a special extract of Crataegus leaves with flowers, on the relaxation of rat aorta and human mammarian artery (coronary bypass patients).
Experiments were performed in the presence and absence (mechanical disruption) of endothelium. In addition, we investigated three fractions of WS(R) 1442 (fraction A: lipophilic, containing flavonoids and oligomeric procyanidins (OPC), fraction B: hydrophilic, containing flavonoids and low molecular weight OPC, fraction C: hydrophilic, essentially flavonoid-free and rich in high molecular weight OPC).
WS 1442 induced a concentration-dependent vasodilation in isolated vessel rings that had been precontracted by 10 microM phenylephrine (concentration for halfmaximal relaxation (IC(50)): rat: 15.1 +/- 0.6 microg/ml (n = 7), human: 19.3 +/- 3.4 microg/ml (n = 6)). The maximal vasorelaxation induced after application of 100 microg of WS 1442 was 75.0 +/- 5.7% (rat) and 79.2 +/- 5.8% (human) of the papaverine (0.1 mM)-induced vasodilation. If the experiments were performed in the presence of L-nitroarginine methylester (10 microM, eNOS-inhibition) or after mechanical disruption of the endothelium, no vasorelaxation was observed in the presence of WS 1442. The vasorelaxant properties of WS 1442 were mediated by fraction C. WS 1442 induced an NO-liberation from human coronary artery endothelial cells as measured by diaminofluorescein. WS 1442 induced eNOS-activation was due to a phosphorylation at serine 1177. No eNOS-translocation or phosphorylation at serine 114 or threonine 495 was observed after application of WS 1442.
It is concluded that WS 1442, induces an endothelium-dependent, NO-mediated vasorelaxation via eNOS phosphorylation at serine 1177.
本研究调查了WS(R) 1442（一种带花山楂叶的特殊提取物）对大鼠主动脉和人乳腺动脉（冠状动脉搭桥患者）舒张的影响。
在内皮存在和不存在（机械破坏）的情况下进行实验。此外，我们研究了WS(R) 1442的三个组分（组分A：亲脂性，含有黄酮类化合物和低聚原花青素（OPC）；组分B：亲水性，含有黄酮类化合物和低分子量OPC；组分C：亲水性，基本不含黄酮类化合物且富含高分子量OPC）。
WS 1442在由10微摩尔苯肾上腺素预收缩的离体血管环中诱导浓度依赖性血管舒张（半数最大舒张浓度（IC(50)）：大鼠：15.1±0.6微克/毫升（n = 7），人：19.3±3.4微克/毫升（n = 6））。应用100微克WS 1442后诱导的最大血管舒张为罂粟碱（0.1毫摩尔）诱导的血管舒张的75.0±5.7%（大鼠）和79.2±5.8%（人）。如果在L-硝基精氨酸甲酯（10微摩尔，内皮型一氧化氮合酶抑制）存在下或在内皮机械破坏后进行实验，则在WS 1442存在下未观察到血管舒张。WS 1442的血管舒张特性由组分C介导。通过二氨基荧光素测量，WS 1442诱导人冠状动脉内皮细胞释放一氧化氮。WS 1442诱导的内皮型一氧化氮合酶激活是由于丝氨酸1177处的磷酸化。应用WS 1442后未观察到内皮型一氧化氮合酶转位或丝氨酸114或苏氨酸495处的磷酸化。
得出结论，WS 1442通过丝氨酸1177处的内皮型一氧化氮合酶磷酸化诱导内皮依赖性、一氧化氮介导的血管舒张。
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