Aldosterone activates vascular p38MAP kinase and NADPH oxidase via c-Src

Callera, G.E., Touyz, R.M. , Tostes, R.C., Yogi, A., He, Y., Malkinson, S. and Schriffin, E.L. (2005) Aldosterone activates vascular p38MAP kinase and NADPH oxidase via c-Src. Hypertension, 45(4), pp. 773-779. (doi: 10.1161/01.HYP.0000154365.30593.d3)

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Increasing evidence indicates that aldosterone elicits vascular effects through nongenomic signaling pathways. We tested the hypothesis that aldosterone induces activation of vascular mitogen-activated protein (MAP) kinases and NADPH oxidase via c-Src–dependent mechanisms in vascular smooth muscle cells (VSMCs). Aldosterone effects on activation of c-Src, p38MAP kinase, and NADPH oxidase, and incorporation of [3H]proline, an index of collagen synthesis, were assessed in cultured rat VSMCs. Studies were performed in the absence and presence of eplerenone, a selective mineralocorticoid receptor blocker, PP2, a selective Src inhibitor, and SB212190, a selective p38MAPK inhibitor. Phosphorylation of c-Src was dose-dependently increased by aldosterone, with maximal responses obtained at 10−7 mol/L. Aldosterone increased p38MAP kinase phosphorylation, NAD(P)H oxidase activation, and [3H]proline incorporation. These responses were abrogated by eplerenone and almost abolished by PP2. Aldosterone-stimulated incorporation of [3H]proline was significantly reduced by SB212190, indicating that p38MAP kinase plays a role in profibrotic actions of aldosterone. To unambiguously demonstrate the importance of aldosterone in c-Src signaling, VSMCs from c-Src+/+ and c-Src+/− mice were also studied. Aldosterone increased phosphorylation of c-Src, p38MAP kinase, and cortactin, a Src-specific substrate, in c-Src+/+ VSMCs, but not in c-Src-deficient cells. Taken together, our findings demonstrate that nongenomic signaling by aldosterone occurs through c-Src–dependent pathways. These processes may play an important role in profibrotic actions of aldosterone.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Callera, G.E., Touyz, R.M., Tostes, R.C., Yogi, A., He, Y., Malkinson, S., and Schriffin, E.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Hypertension
ISSN (Online):1524-4563
Published Online:07 February 2005

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