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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., Fiebeler, A., Muller, D.N., Park, J.K., Shagdarsuren, E., Lindschau, C., Dechend, R., Viedt, C., Pilz, B., 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
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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