Pulsatile stretch and shear stress: Physical stimuli determining the production of endothelium-derived relaxing factors

Pulsatile stretch and shear stress: Physical stimuli determining the production of endothelium-derived relaxing factors
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DOI:
10.1159/000025568
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发表时间:
1998-03-01
影响因子:
1.7
通讯作者:
Fleming, I
Fleming, I
中科院分区:
医学4区
文献类型:
--
作者:
Busse, R;Fleming, I

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由流体剪切应力和脉动拉伸在内皮处产生的机械力在确保血管活性内皮自分泌物的连续释放方面是重要的。尽管内皮细胞能够检测这些物理刺激并将其转化为化学信号的机制尚不清楚,但该过程涉及整合素、G蛋白和蛋白激酶级联的活化,组成型内皮型一氧化氮合酶(NOS III),分类为钙/钙调素依赖性亚型,在[Ca 2 +]缺乏持续增加的情况下,可被剪切应力和等长收缩激活(i)通过涉及其在细胞骨架内重新分布的机制,因此,似乎由Ca 2+升高受体依赖性激动剂(例如缓激肽)和血液动力学刺激激活的细胞内级联是不同的,有节奏的血管扩张也能引起超氧阴离子和内皮细胞的合成-衍生的超极化因子,其在调节某些血管床中的动脉顺应性中起作用。
Mechanical forces generated at the endothelium by fluid shear stress and pulsatile stretch are important in ensuring the continuous release of vasoactive endothelial autacoids, Although the mechanism by which endothelial cells are able to detect and convert these physical stimuli into chemical signals is unclear, this process involves the activation of integrins, G proteins and cascades of protein kinases, The constitutive endothelial nitric oxide synthase (NOS III), classified as a Ca2+/calmodulin-dependent isoform, can be activated by shear stress and isometric contraction in the absence of a maintained increase in [Ca2+](i) via a mechanism involving its redistribution within the cytoskeleton/caveolae and the activation of one or more regulatory NOS-associated proteins, Thus it would appear that the intracellular cascades activated by Ca2+-elevating receptor-dependent agonists, such as bradykinin, and hemodynamic stimuli are distinct, Rhythmic vessel distension is also able to elicit the synthesis of superoxide anions and the endothelium-derived hyperpolarizing factor which play a role in modulating arterial compliance in certain vascular beds.