Circulation. 2004;109:2792-2800
Published online before print May 24, 2004, doi: 10.1161/01.CIR.0000131860.80444.AB
Published online before print May 24, 2004, doi: 10.1161/01.CIR.0000131860.80444.AB
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(Circulation. 2004;109:2792-2800.)
© 2004 American Heart Association, Inc.
Basic Science Reports |
Aldosterone Potentiates Angiotensin II–Induced Signaling in Vascular Smooth Muscle Cells
From Medical Faculty of the Charité, Franz Volhard Clinic, HELIOS Klinikum-Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany (I.M., A.F., D.N.M., E.S., R.D., B.P., F.C.L.); the Department of Internal Medicine and Nephrology, Hannover University Medical School, Hannover, Germany (J.-K.P., C.L., H.H.); and the Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany (C.V.).
Correspondence to Friedrich C. Luft, Wiltberg Strasse 50, 13125 Berlin, Germany. E-mail luft{at}fvk-berlin.de
Received February 10, 2003; de novo received October 14, 2003; revision received February 10, 2004; accepted February 24, 2004.
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.
Key Words: angiotensin • aldosterone • receptors • kinases • reactive oxygen species
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|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
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|
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