Aldosterone: effects on the kidney and cardiovascular system.
Aldosterone, a steroid hormone with mineralocorticoid activity, is mainly recognized for its action on sodium reabsorption in the distal nephron of the kidney, which is mediated by the epithelial sodium channel (ENaC). Beyond this well-known action, however, aldosterone exerts other effects on the kidney, blood vessels and the heart, which can have pathophysiological consequences, particularly in the presence of a high salt intake. Aldosterone is implicated in renal inflammatory and fibrotic processes, as well as in podocyte injury and mesangial cell proliferation. In the cardiovascular system, aldosterone has specific hypertrophic and fibrotic effects and can alter endothelial function. Several lines of evidence support the existence of crosstalk between aldosterone and angiotensin II in vascular smooth muscle cells. The deleterious effects of aldosterone on the cardiovascular system require concomitant pathophysiological conditions such as a high salt diet, increased oxidative stress, or inflammation. Large interventional trials have confirmed the benefits of adding mineralocorticoid-receptor antagonists to standard therapy, in particular to angiotensin-converting-enzyme inhibitor and angiotensin II receptor blocker therapy, in patients with heart failure. Small interventional studies in patients with chronic kidney disease have shown promising results, with a significant reduction of proteinuria associated with aldosterone antagonism, but large interventional trials that test the efficacy and safety of mineralocorticoid-receptor antagonists in chronic kidney disease are needed.
Briet
Marie
M
Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital and Lady Davis Institute for Medical Research, McGill University, 3755 Côte-Ste-Catherine Road, Montreal, QC H3T 1E2, Canada.
Schiffrin
Ernesto L
EL
D000450:Aldosterone / Q000009:adverse effects* / Q000494:pharmacology* / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004730:Endothelium, Vascular / Q000187:drug effects; D005355:Fibrosis / Q000139:chemically induced / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D018384:Oxidative Stress; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D012982:Sodium, Dietary / Q000009:adverse effects / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D015222:Sodium Channels; D012982:Sodium, Dietary; D000450:Aldosterone