Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II.
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.
Zou
Yunzeng
Y
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Akazawa
Hiroshi
H
Qin
Yingjie
Y
Sano
Masanori
M
Takano
Hiroyuki
H
Minamino
Tohru
T
Makita
Noriko
N
Iwanaga
Koji
K
Zhu
Weidong
W
Kudoh
Sumiyo
S
Toko
Haruhiro
H
Tamura
Koichi
K
Kihara
Minoru
M
Nagai
Toshio
T
Fukamizu
Akiyoshi
A
Umemura
Satoshi
S
Iiri
Taroh
T
Fujita
Toshiro
T
Komuro
Issei
I
D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D019556:COS Cells; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology; D003600:Cytosol / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D013314:Stress, Mechanical; D013777:Tetrazoles / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D010716:Phosphatidylinositols; D011518:Proto-Oncogene Proteins; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000804:Angiotensin II; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; C081643:candesartan