Extra-adrenal aldosterone synthesis and its role in non-classical target tissues
C Delcayre, C Heymes, J Nehme, ML Ambroisine, E Robidel, N De Angelis & P Milliez
Aldosterone (Aldo) plays a crucial role in heart remodeling. 1) In presence of high sodium, Aldo induces fibrosis in the cardiovascular system by still partly unknown mechanisms. Aldo-salt induces a pericoronary inflammatory phenotype, that may be one of the first events leading to fibrosis. The RALES trial has evidenced a beneficial effect of spironolactone on both mortality and morbidity in heart failure (HF), that are linked to a reduction of cardiac fibrosis. 2) In rat heart, StAR and the Aldo-synthase (AS) are present and Aldo is produced at low level and increased by Ang II. This production nevertheless results in high local Aldo concentrations. 3) In rat myocardial infarction Aldo production is increased and it participates to the left ventricle fibrosis. 4) Unpublished results from our laboratory indicate that male mice overexpressing the AS gene in heart have a major coronary dysfunction. 5) In human species, cardiac Aldo production is very low but it is strongly increased in HF.
Thus, in HF increased adrenal and cardiovascular productions of Aldo (as part of the neurohormonal reaction) have detrimental consequences on cardiac function. Aldo effects on coronary function and pericoronary structure and on the induction of tissular fibrosis are key factors to explain these detrimental consequences.