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Adrenomedullin inhibits Angiotensin II‐induced ROS production Via modulation of Src activation
Author(s) -
Liu Jing,
shimosawa tatsuo,
Matsui Hiromitsu,
Supowit Scott,
Dipette Donald,
Ando Katsuyuki,
Fujita Toshiro
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb69-b
Subject(s) - adrenomedullin , angiotensin ii , chemistry , medicine , endocrinology , reactive oxygen species , nadph oxidase , vascular smooth muscle , proto oncogene tyrosine protein kinase src , receptor , oxidative stress , biology , biochemistry , smooth muscle
We have demonstrated that adrenomedullin protects against angiotensin II‐induced cardiovascular damage through the inhibition of increased oxidative stress production in adrenomedullin deficient mice□However, the mechanisma that underlie this activity remain to be elucidated. We therefore, investigated the effect of adrenomedullin on angiotensin II stimulated reactive oxygen species production and related signaling pathway in cultured rat aortic vascular smooth muscle cells (VSMCs)□Angiotensin II markedly increased ROS production through activation of NADPH oxidase. This effect was attenuated by adrenomedullin in a concentration‐dependent manner (10 −8 –10 −6 mol/L)□The inhibitory effect of adrenomedullin was lost following expression of a constitutive‐active Src□Moreover, adrenomedullin intersected angiotensin II signaling by inducing Csk activation and thus inhibiting Src phosphorylation□The effect of adrenomedullin was mimicked by dibutyl‐cAMP and abolished by the pretreatment with H‐89, a protein kinase A inhibitor, and CGRP(8–37), an adrenomedullin/CGRP receptor antagonist□These data, for the first time demostrated that adrenomedullin attenuates, at least in part, the angiotensin II‐induced ROS production in VSMCs via activation of Csk thereby inhibiting Src phosphorylation.