Artikel
Aldosterone potentiates angiotensin II-induced signaling in vascular smooth muscle cells
Aldosteron potenziert die Angiotensin II-vermittelte Signaltransduktion in glatten Muskelzellen
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Autoren
Veröffentlicht: | 11. November 2004 |
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Gliederung
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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 with only a small effect on blood pressure. How Ang II and aldosterone (Ald) might interact is ill defined.
Methods and Results
We investigated the effects of Ang II (10-7 M) and Ald (10-7 M) on extracellular regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling in vascular smooth muscle cells (VSMC) with western blotting and confocal microscopy. Ang II induced ERK 1/2 and JNK phosphorylation by 2 min. Ald achieved the same by 10 min. Ang II+Ald had a potentiating effect by 2 min. The oxygen radical scavengers gluthatione (GSH) and Tiron as well as the specific epidermal growth factor (EGF) receptor antagonist AG1478, markedly reduced the Ang II-, Ald-, and combination-induced ERK1/2 phosphorylation. Preincubating the cells with the MR blocker spironolactone (Spi; 10-6 M) abolished Ang II-induced ERK1/2 phosphorylation.
Conclusion
Ald potentiates Ang II-induced ERK-1/2 and JNK phosphorylation. Oxygen radicals, the MR, and the EGF receptor play a role in early signaling induced by Ang II and Ald in VSMC. These in vitro data may help explain the effects of MR blockade on Ang II-induced end-organ damage in vivo.