Article abstract
Nature Cell Biology 6, 499 - 506 (2004)
Published online: 16 May 2004 | Corrected online: 25 June 2004 | doi:10.1038/ncb1137
Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II
Yunzeng Zou1, Hiroshi Akazawa1, Yingjie Qin1, Masanori Sano1, Hiroyuki Takano1, Tohru Minamino1, Noriko Makita2, Koji Iwanaga1, Weidong Zhu1, Sumiyo Kudoh3, Haruhiro Toko1, Koichi Tamura4, Minoru Kihara4, Toshio Nagai1, Akiyoshi Fukamizu5, Satoshi Umemura4, Taroh Iiri2, Toshiro Fujita2 & Issei Komuro1
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.
- Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
- Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
- Department of Cardiology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-cho, Kawakita, Ishikawa 920-0265, Japan.
- Department of Internal Medicine II, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
- Center for Tsukuba Advanced Research Alliance, Institute of Applied Biochemistry, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8577, Japan.
Correspondence to: Issei Komuro1 e-mail: komuro-tky@umin.ac.jp
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