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- Glaucia E. Callera
- From CIHR Multidisciplinary Research Group on Hypertension (G.E.C., R.M.T., Y.H., S.M., E.L.S.), Clinical Research Institute of Montreal, University of Montreal, Canada; and the Department of Pharmacology (R.C.T., A.Y.), Institute of Biomedical Sciences, University of Sao Paulo, Brazil.
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- Rhian M. Touyz
- From CIHR Multidisciplinary Research Group on Hypertension (G.E.C., R.M.T., Y.H., S.M., E.L.S.), Clinical Research Institute of Montreal, University of Montreal, Canada; and the Department of Pharmacology (R.C.T., A.Y.), Institute of Biomedical Sciences, University of Sao Paulo, Brazil.
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- Rita C. Tostes
- From CIHR Multidisciplinary Research Group on Hypertension (G.E.C., R.M.T., Y.H., S.M., E.L.S.), Clinical Research Institute of Montreal, University of Montreal, Canada; and the Department of Pharmacology (R.C.T., A.Y.), Institute of Biomedical Sciences, University of Sao Paulo, Brazil.
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- Alvaro Yogi
- From CIHR Multidisciplinary Research Group on Hypertension (G.E.C., R.M.T., Y.H., S.M., E.L.S.), Clinical Research Institute of Montreal, University of Montreal, Canada; and the Department of Pharmacology (R.C.T., A.Y.), Institute of Biomedical Sciences, University of Sao Paulo, Brazil.
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- Ying He
- From CIHR Multidisciplinary Research Group on Hypertension (G.E.C., R.M.T., Y.H., S.M., E.L.S.), Clinical Research Institute of Montreal, University of Montreal, Canada; and the Department of Pharmacology (R.C.T., A.Y.), Institute of Biomedical Sciences, University of Sao Paulo, Brazil.
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- Sam Malkinson
- From CIHR Multidisciplinary Research Group on Hypertension (G.E.C., R.M.T., Y.H., S.M., E.L.S.), Clinical Research Institute of Montreal, University of Montreal, Canada; and the Department of Pharmacology (R.C.T., A.Y.), Institute of Biomedical Sciences, University of Sao Paulo, Brazil.
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- Ernesto L. Schiffrin
- From CIHR Multidisciplinary Research Group on Hypertension (G.E.C., R.M.T., Y.H., S.M., E.L.S.), Clinical Research Institute of Montreal, University of Montreal, Canada; and the Department of Pharmacology (R.C.T., A.Y.), Institute of Biomedical Sciences, University of Sao Paulo, Brazil.
抄録
<jats:p> 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 [ <jats:sup>3</jats:sup> H]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 <jats:sup>−7</jats:sup> mol/L. Aldosterone increased p38MAP kinase phosphorylation, NAD(P)H oxidase activation, and [ <jats:sup>3</jats:sup> H]proline incorporation. These responses were abrogated by eplerenone and almost abolished by PP2. Aldosterone-stimulated incorporation of [ <jats:sup>3</jats:sup> H]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 <jats:sup>+/+</jats:sup> and c-Src <jats:sup>+/−</jats:sup> mice were also studied. Aldosterone increased phosphorylation of c-Src, p38MAP kinase, and cortactin, a Src-specific substrate, in c-Src <jats:sup>+/+</jats:sup> 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. </jats:p>
収録刊行物
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- Hypertension
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Hypertension 45 (4), 773-779, 2005-04
Ovid Technologies (Wolters Kluwer Health)
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キーワード
詳細情報 詳細情報について
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- CRID
- 1363670319995880832
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- NII論文ID
- 30022678622
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- ISSN
- 15244563
- 0194911X
- http://id.crossref.org/issn/0194911X
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- データソース種別
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- Crossref
- CiNii Articles