Corder Roger, Warburton Richard C, Khan Noorafza Q, Brown Ruth E, Wood Elizabeth G, Lees Delphine M
William Harvey Research Institute, Barts and the London, Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK.
Clin Sci (Lond). 2004 Nov;107(5):513-7. doi: 10.1042/CS20040189.
Reduced endothelium-dependent vasodilator responses with increased synthesis of ET-1 (endothelin-1) are characteristics of endothelial dysfunction in heart failure and are predictive of mortality. Identification of treatments that correct these abnormalities may have particular benefit for patients who become refractory to current regimens. Hawthorn preparations have a long history in the treatment of heart failure. Therefore we tested their inhibitory effects on ET-1 synthesis by cultured endothelial cells. These actions were compared with that of GSE (grape seed extract), as the vasoactive components of both these herbal remedies are mainly oligomeric flavan-3-ols called procyanidins. This showed extracts of hawthorn and grape seed were equipotent as inhibitors of ET-1 synthesis. GSE also produced a potent endothelium-dependent vasodilator response on preparations of isolated aorta. Suppression of ET-1 synthesis at the same time as induction of endothelium-dependent vasodilation is a similar response to that triggered by laminar shear stress. Based on these results and previous findings, we hypothesize that through their pharmacological properties procyanidins stimulate a pseudo laminar shear stress response in endothelial cells, which helps restore endothelial function and underlies the benefit from treatment with hawthorn extract in heart failure.
内皮素 -1（ET -1）合成增加导致内皮依赖性血管舒张反应减弱是心力衰竭患者内皮功能障碍的特征，并且可预测死亡率。确定能够纠正这些异常情况的治疗方法可能对那些对当前治疗方案产生耐药性的患者具有特殊益处。山楂制剂在心力衰竭治疗方面有着悠久的历史。因此，我们测试了它们对培养的内皮细胞合成ET -1的抑制作用。将这些作用与葡萄籽提取物（GSE）进行比较，因为这两种草药疗法的血管活性成分主要是称为原花青素的低聚黄烷 -3 -醇。结果表明，山楂和葡萄籽提取物作为ET -1合成抑制剂的效力相当。GSE对离体主动脉制剂也产生了强烈的内皮依赖性血管舒张反应。在诱导内皮依赖性血管舒张的同时抑制ET -1合成与层流切应力引发的反应相似。基于这些结果和先前的研究发现，我们推测原花青素通过其药理特性在内皮细胞中刺激了一种假层流切应力反应，这有助于恢复内皮功能，并构成了山楂提取物治疗心力衰竭有益效果的基础。
