Aldosterone, a well-established hormone in blood pressure and electrolyte control, has recently been shown to also play a key role in cardiovascular and renal injury; however, the underly-ing mechanisms are not well understood. Because the epider-mal growth factor receptor (EGFR) - as a heterologous signal transducer -is involved in the development of vascular fibrosis and hypertrophy by angiotensin II or endothelin, upregulation of EGFR expression and EGFR transactivation by aldosterone-bound mineralocorticoid receptor (MR) are attractive hypothe-sis.

(i) In cultured vascular smooth muscle cells (VSMC) as well as in cells transfected with MR aldosterone stimulates ERK1/2 phosphorylation via EGFR transactivation. Thus, non-genotropic actions of aldosterone involve, at least in part, MR-mediated EGFR transactivation. (ii) Aldosterone stimulates the expression of EGFR in vascular tissue in vivo and in cultured VSMC. These effects can be reproduced in heterologous MR expression systems. Activated MR stimulates the EGFR pro-motor, most probably via a direct protein-DNA-interaction. (iii) These pathways seem to contribute to the mitogenic action of aldosterone in VSMC and may also lead to the disturbed extracellular matrix homeostasis (enhanced collagen and fi-bronectin deposition). (iv) Since the EGFR is also a target for angiotensin II, this receptor can explain part of the pathological synergism between aldosterone and angiotensin II.