Aldosterone and the heart: towards a physiological function?

1. Introduction progesterone and androgen receptors. The functional and structural organization of this receptor family displays Aldosterone (Aldo) plays an essential role in regulation three main domains: the variable N-terminal region, a of body sodium and potassium homeostasis by acting on well-conserved cysteine-rich DNA-binding domain (590% epithelial tissues such as kidney and colon. Since about ten amino acid identity) and a C-terminal steroid binding years the two dogmas which classically characterize Aldo, domain (550% amino acid identity). In addition to epi-i.e., a synthesis in adrenal glands only and an action thelial tissues (kidney, parotid gland and colon) and non-exclusively in epithelial tissues, have been challenged. epithelial tissues as brain and blood vessels, both the Namely, Aldo receptors are present in the heart and mRNA and protein MR have been found in rodent and specific actions of Aldo can be demonstrated in this organ. human hearts [3,4]. In situ hybridization indicates that MR This suggests that cardiac tissue may be a genuine target is expressed in cardiomyocytes, endothelial cells and for Aldo. Moreover, there are indications that an increase fibroblasts [4]. In contrast, neither mRNA nor immuno-of plasma Aldo may be a risk factor in cardiovascular reactive MR was detected over small intramyocardial pathologies. For example, the CONSENSUS multicentric blood vessels in rabbit and human heart [4]. study has shown a relationship between plasma Aldo concentration and mortality in patients with congestive heart failure [1] The very recent discovery of Aldo 2.2. MR specificity for Aldo synthesis in rat heart [2] brings a new step to the evolution of our ideas concerning the physiology of this hormone. The high amino acid sequence identity in the ligand This demonstrates the existence of an Aldo tissular system binding domains of MR and GR leads to substantial – i.e., the presence in a cell or a group of cells of all the binding of glucocorticoids to MR. As circulating con-biochemical elements necessary for synthesis of a hormone centrations of glucocorticoids are commonly three orders and its specific receptors – making it possibly a local of magnitude higher than those of Aldo, specific binding of autocrine or paracrine action. This review makes the point Aldo to the MR involves several mechanisms. First, the of the literature dealing with effects and synthesis of Aldo NAD-dependent enzyme 11b-hydroxysteroid dehydrogen-in the heart. ase 2 (11b-HSD2) converts cortisol and corticosterone into cortisone and 11-dehydrocorticosterone, respectively, which have negligible affinity …