P-343: Aldosterone activates ERK1/2 and p38map kinase in vascular smooth muscle cells by nongenomic mechanisms in WKY and SHR – role of endothelin-1

• Published in: American journal of hypertension 2004-05, Vol.17 (S1), p.159A-159A
• Main Authors: Touyz, R.M., Malkinson, S., Yao, G., Endemann, D., Schiffrin, E.L.
• Format: Article
• Language: English
• Subjects: Aldosterone; Signal Transduction; Vascular Smooth Muscle Cells
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/j.amjhyper.2004.03.418

Increasing evidence indicates that aldosterone induces rapid signaling events through non-genomic pathways. Mechanisms whereby aldosterone induces these effects are unclear. In the present study we investigated short-term actions of aldosterone on mitogen-activated protein (MAP) kinase signaling in vascular smooth muscle cells (VSMC) from WKY and SHR and assessed whether these processes are influenced by endothelin-1. Cultured VSMCs derived from mesenteric arteries of adult WKY and SHR were studied. Activation of ERK1/2 and p38 MAP kinase was assessed by Western blot, using phospho-specific antibodies. Spironolactone, a non-specific mineralocorticoid receptor blocker, and eplerenone, a specific aldosterone receptor blocker were used to inhibit aldosterone-mediated effects. The role of ET-1 in aldosterone signaling was evaluated with the ETA/ETB receptor blocker, bosentan. Aldosterone time-dependently increased ERK1/2 and p38MAP kinase phosphorylation in WKY and SHR. Responses were maximal within 15 mins and were sustained for up to 60 mins. Spironolactone and eplerenone did not significantly influence aldosterone-elicited effects, whereas bosentan significantly reduced aldosterone-mediated phosphorylation of ERK1/2 and p38MAP kinase. Spironolactone alone significantly increased activation of MAP kinases in WKY and SHR. Aldosterone rapidly activates ERK1/2 and p38MAP kinase in VSMCs. These effects are not mediated via classical mineralocorticoid receptors, but appear to involve an ET-1-sensitive component. Our data suggest that aldosterone activates MAP kinases in VSMCs from WKY and SHR through non-genomic, ETA/ETB-mediated pathways. Am J Hypertens (2004) 17, 159A–159A; doi: 10.1016/j.amjhyper.2004.03.418