Aldosterone action in the heart

Mineralocorticoid receptor is essential for corticosteroid-induced up-regulation of L-type calcium currents in cultured neonatal cardiomyocytes

“…This is based on two main lines of evidence. Firstly, the EC50 value for the effect aldosterone on I Ca was 2 nM, which is within the 0.1-2 nM range of MRdependent aldosterone effects determined in different studies [2]. Secondly, these effects were abolished in myocytes of MR-deficient mice, but conserved in GRdeficient cells.…”

“…We also observed that the glucocorticoid corticosterone increased the I Ca , similarly to aldosterone. Under physiologic conditions, it is very likely that the MR is continuously occupied by the circulating glucocorticoids when one considers that (1) in cardiomyocytes, the MR is "unprotected" because of the low 11β-HSD2 activity, (2) …”

“…The natural mineralocorticoid aldosterone and the glucocorticoid cortisol (corticosterone in rodents) bind to intracellular receptors, the high affinity MR, and the low affinity GR, which are both expressed in cardiomyocytes [2]. However, cardiomyocytes are defined as "nonclassical" MR-expressing cells because the ligand specificity (aldosterone vs cortisol/corticosterone) of the receptor remains unclear.…”

“…However, cardiomyocytes are defined as "nonclassical" MR-expressing cells because the ligand specificity (aldosterone vs cortisol/corticosterone) of the receptor remains unclear. While in classical MR-expressing tissues, such as the kidney and the colon, the MR is protected from occupancy by glucocorticoids by the activity of the 11-β-hydroxysteroid-dehydrogenase type-2 (11β-HSD2) that converts cortisol/corticosterone into inactive metabolites; cardiomyocytes demonstrate very low levels of this enzyme [2]. This observation suggests that there is very little, if any, "MR-protection" mechanism, which may circumvent MR occupancy by glucocorticoids circulating at concentrations >100-fold higher than aldosterone.…”

Mineralocorticoid Receptor Antagonism Prevents the Electrical Remodeling That Precedes Cellular Hypertrophy After Myocardial Infarction

“…Collectively, different animal 35 and clinical 4 studies have emphasized the pathophysiological cardiac role of MRs. One of the more striking results of the resurgent use of the aldosterone-blocking agent spironolactone or its analogue eplerenone to treat patients with systolic LV dysfunction has been a reduction in the incidence of arrhythmias, which have been mainly related to fibrosis. 4,8,9,35 However, other protective mechanisms have been underscored. Aldosterone is the major regulator of body ion homeostasis.…”