title: Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II.
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.
authors.affiliation: Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akazawa
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Qin
authors.forename: Masanori
authors.initials: M
authors.lastname: Sano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takano
authors.forename: Tohru
authors.initials: T
authors.lastname: Minamino
authors.forename: Noriko
authors.initials: N
authors.lastname: Makita
authors.forename: Koji
authors.initials: K
authors.lastname: Iwanaga
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhu
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Kudoh
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Toko
authors.forename: Koichi
authors.initials: K
authors.lastname: Tamura
authors.forename: Minoru
authors.initials: M
authors.lastname: Kihara
authors.forename: Toshio
authors.initials: T
authors.lastname: Nagai
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
authors.forename: Taroh
authors.initials: T
authors.lastname: Iiri
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: 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*
chemical_list: 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