Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II
Top Cited Papers
- 16 May 2004
- journal article
- research article
- Published by Springer Nature in Nature Cell Biology
- Vol. 6 (6) , 499-506
- https://doi.org/10.1038/ncb1137
Abstract
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.Keywords
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