The new biology of aldosterone.
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.
MRC Blood Pressure Group, Division of Cardiovascular and Medical Sciences, University of Glasgow, Gardiner Institute, Western Infirmary, Glasgow G11 6NT, UK. j.connell@clinmed.gla.ac.uk
John M C
JM
Connell
Eleanor
E
Davies
D000450:Aldosterone / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000502:physiology*; D002490:Central Nervous System / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D009206:Myocardium / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology; D015384:Zona Glomerulosa / Q000378:metabolism
D015415:Biomarkers; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone