Key result
Nitric oxide production prevented AngII-induced vascular smooth muscle cell hypertrophy and protein synthesis by inhibiting RhoA translocation to caveolae and ROS formation in rat aortic rings.
Nitric oxide inhibits AngII-induced vascular smooth muscle cell hypertrophy by preventing RhoA translocation to caveolae and reducing ROS formation.
Does not change clinical practice; leaves open translation of NO-RhoA pathway to human vascular disease.
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.
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Hussein et al. (2014) studied Vascular hypertrophy. NO donor S-nitroso-nacetylpenicillamine (SNAP), ROCK inhibitor, RhoA inhibitor, or methyl-B-cyclodextrin vs. AngII (1 nM) alone was evaluated on AngII-induced VSMC hypertrophy, protein synthesis, and RhoA translocation. Nitric oxide production prevented AngII-induced vascular smooth muscle cell hypertrophy and protein synthesis by inhibiting RhoA translocation to caveolae and ROS formation in rat aortic rings.
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