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Aldosterone potentiates angiotensin II-induced signaling in vascular smooth muscle cells

Item Type:Article
Title:Aldosterone potentiates angiotensin II-induced signaling in vascular smooth muscle cells
Creators Name:Mazak, I. and Fiebeler, A. and Muller, D.N. and Park, J.K. and Shagdarsuren, E. and Lindschau, C. and Dechend, R. and Viedt, C. and Pilz, B. and Haller, H. and Luft, F.C.
Abstract:Background - In a double-transgenic human renin and human angiotensinogen rat model, we found that mineralocorticoid receptor (MR) blockade ameliorated angiotensin II (Ang II)-induced renal and cardiac damage. How Ang II and aldosterone (Ald) might interact is ill defined. Methods and Results - We investigated the effects of Ang II (10-7 mol/L) and Ald (10 -7 mol/L) on extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling in vascular smooth muscle cells (VSMCs) with Western blotting and confocal microscopy. Ang II induced ERK 1/2 and JNK phosphorylation by 2 minutes. Ald achieved the same at 10 minutes. Ang II + Ald had a potentiating effect by 2 minutes. Two oxygen radical scavengers and the epidermal growth factor receptor (EGFR) antagonist AG1478 reduced Ang II-, Ald-, and combination-induced ERK1/2 phosphorylation. Preincubating the cells with the MR blocker spironolactone (10-6 mol/L) abolished Ang II-induced ROS generation, EGFR transactivation, and ERK1/2 phosphorylation. Conclusions - Ald potentiates Ang II-induced ERK-1/2 and JNK phosphorylation. Oxygen radicals, the MR, and the EGFR play a role in early signaling induced by Ang II and Ald in VSMCs. These in vitro data may help explain the effects of MR blockade on Ang II-induced end-organ damage in vivo.
Keywords:Angiotensin, Aldosterone, Reactive Oxygen Species, Receptors, Kinases, Animals, Rats
Source:Circulation
ISSN:0009-7322
Publisher:American Heart Association (U.S.A.)
Volume:109
Number:22
Page Range:2792-2800
Date:8 June 2004
Official Publication:https://doi.org/10.1161/01.CIR.0000131860.80444.AB
PubMed:View item in PubMed

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