Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II
Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II
复制标题
DOI：
10.1038/ncb1137
复制
发表时间：
2004-06-01
影响因子：
21.3
通讯作者：
Komuro, I
中科院分区：
文献类型：
--
作者：
Zou, YZ;Akazawa, H;Komuro, I
血管紧张素II 1型（AT1）受体在负荷诱导的心肌肥厚中起着至关重要的作用。在这里，我们表明，AT1受体可以通过机械应力激活血管紧张素II的独立机制。在没有血管紧张素II参与的情况下，机械应力不仅在体外激活细胞外信号调节激酶并增加磷酸肌醇的产生，而且在体内诱导心脏肥大。机械牵张诱导AT1受体与Janus激酶2的结合，以及G蛋白向胞质中的易位。所有这些事件都被AT1受体阻滞剂坎地沙坦抑制。因此，机械应力激活AT 1受体独立于血管紧张素II，这种激活可以被AT 1受体的反向激动剂抑制。
The angiotensin II type 1 (AT1) receptor has a crucial role in load-induced cardiac hypertrophy. Here we show that the AT1 receptor can be activated by mechanical stress through an angiotensin-II-independent mechanism. Without the involvement of angiotensin II, mechanical stress not only activates extracellular-signal-regulated kinases and increases phosphoinositide production in vitro, but also induces cardiac hypertrophy in vivo. Mechanical stretch induces association of the AT1 receptor with Janus kinase 2, and translocation of G proteins into the cytosol. All of these events are inhibited by the AT1 receptor blocker candesartan. Thus, mechanical stress activates AT1 receptor independently of angiotensin II, and this activation can be inhibited by an inverse agonist of the AT1 receptor.