The new biology of aldosterone

Abstract

Classically, aldosterone is synthesised in the adrenal zona glomerulosa and binds to specific mineralocorticoid receptors located in the cytosol of target epithelial cells. Translocation of the resulting steroid receptor complex to the cell nucleus modulates gene expression and translation of specific 'aldosterone-induced' proteins that regulate electrolyte and fluid balance. However, non-epithelial and rapid non-genomic actions of aldosterone have also been described that account for a variety of actions of aldosterone that contribute to blood pressure homeostasis. These include key actions on endothelial cells and on cardiac tissue.There is also evidence that aldosterone can be synthesised in other tissues; the most convincing evidence relates to the central nervous system. However, suggestions that aldosterone is produced in the heart remain controversial, and adrenal derived aldosterone is the principal source of circulating and locally available hormone.Recent studies have shown major therapeutic benefits of mineralocorticoid receptor antagonism in cardiac failure, which emphasise the importance of aldosterone in causing adverse cardiovascular pathophysiological effects. Additional evidence demonstrates that aldosterone levels predict development of high blood pressure in normotensive subjects, while it is now clear that increased aldosterone action contributes to hypertension and cardiovascular damage in approximately 10% of patients with established hypertension.These new findings highlight the role of aldosterone as a key cardiovascular hormone and extend our understanding of its role in determining adverse cardiovascular outcomes.

Increased Expression of Mineralocorticoid Receptor and 11β‐Hydroxysteroid Dehydrogenase Type 2 in Human Atria During Atrial Fibrillation

“…3 Patients with primary hyperaldosteronism have an increased incidence of AF compared with age, gender, and blood pressure matched controls with essential hypertension. 4 Aldosterone promotes adverse cardiac structural remodeling via cellular proliferation and induces myocardial and vascular fibrosis by binding MR. 19 Our results indicate that MR expression increased at the mRNA and protein level in patients with AF. The MR was mainly localized in the myocardial cell cytoplasm of atrial tissue.…”

“…10,19 Various epithelial cells, vascular smooth muscle cells (VSMCs), and cardiomyocyte express MR. But the difference between epithelial (and VSMC) and nonepithelial MRs, such as myocardial cell MRs, is their response to occupancy by endogenous glucocorticoids.…”

“…In epithelia, glucocorticoids mimic aldosterone, as in AME. 10,19 In nonepithelial tissue such as cardiomyocytes, glucocorticoids do not activate MR, but act as antagonists. 10,19 Although the mechanism underlying this difference is unknown, it may reflect tissue-specific differences in coactivator/corepressor recruitment by MR/glucocorticoid complexes.…”

Plasma Renin Activity and Aldosterone Concentrations in Hypertensive Cats with and without Azotemia and in Response to Treatment with Amlodipine Besylate

“…A recent study suggests that bilateral adrenocortical hyperplasia is an almost ubiquitous finding in cats >9 years (97%), but there was no significant difference in histopathologic grading between hypertensive (n = 37) and normotensive cats (n = 30), supporting that adrenocortical hyperplasia is unlikely to be a primary factor in feline hypertension 13. A number of other factors have been demonstrated to modulate aldosterone production apart from angiotensin II including extracellular potassium concentration, adrenocorticotropic hormone, adrenomedullin, atrial natriuretic peptide, dopamine, endogenous digitalis‐like factors (eg, ouabain) and endothelin‐1, but the effect these play in regulating aldosterone production in the cat has not been investigated 24, 25, 26, 27, 28, 29…”

Variation in adrenal and thyroid hormones with life-history stage in juvenile northern elephant seals (Mirounga angustirostris)

“…Catecholamines, such as epinephrine and norepinephrine, are also released as part of the fight-or-flight response to stress. Together, the suite of hormones activated by this response influence many processes in the body including heart rate, metabolic rate, energy allocation, growth, reproduction, immune response, memory, and behavior, allowing an animal to react appropriately to the stress, which ultimately promotes survival (Breuner et al, 2013;Brilion et al, 1995;Connell and Davies, 2005;Khani and Tayek, 2001;Maule et al, 1987;Romero and Butler, 2007;Tilbrook et al, 2000).…”