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Nitric oxide inhibits vascular remodeling by decreasing angiotensin II‐induced RhoA translocation to caveolae and ROS formation (867.6)
Author(s) -
Hajj Hussein Inaya,
Nourddine Ward,
Soudani Nadia,
Zeidan Asad
Publication year - 2014
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.28.1_supplement.867.6
Subject(s) - rhoa , angiotensin ii , caveolae , chemistry , vascular smooth muscle , microbiology and biotechnology , snap , rho associated protein kinase , medicine , endocrinology , phosphorylation , receptor , signal transduction , biochemistry , biology , smooth muscle , computer graphics (images) , computer science
Decreased production of nitric oxide (NO) leads to induce vascular smooth muscle cell (VSMC) hypertrophy via angiotensin II (AngII) receptors. However, the regulatory mechanism of NO activity on Ang II‐mediated VSMC remodeling remains fully unclear. Here we hypothesized that caveolin‐1 (cav1) and NO production are involved in the regulation of AngII‐induced VSMC remodeling via inhibition of the RhoA translocation to caveolae. Rat aortic rings were cultured in the presence of AngII (1 nM) with or without the NO donor S‐nitroso‐nacetylpenicillamine (100 μM; SNAP), the ROCK inhibitor (10 μM; Y‐27632), the RhoA inhibitor C3 exoenzyme (3 ng/ml; C3), or methyl‐B‐cyclodextrin (10 mM; MBCD). AngII‐induced VSMC hypertrophy and protein synthesis were inhibited by pre‐treatment with SNAP, Y‐27632, C3 or MBCD. AngII‐induced protein synthesis was associated with increased in ROS formation and expression of cav‐1 (2 folds), NADPH oxidase1 (NOX1; 4 folds) and NOX3 (5 folds) and decreased NOX2 (2 folds) expression and NO activity (3 folds). Treatment of the aortic ring with AngII for 20 min increased caveolae‐bound RhoA (4‐folds), cofilin‐2 phosphorylation (3 folds), and F‐ to G‐actin ratio (2 folds), which were prevented by increased of NO production. These results will allow for the creation of pharmacological agents for the treatment of vascular hypertrophy due to AngII.