title: Aldosterone and end-organ damage.
abstract: OBJECTIVE
  This review highlights recent clinical studies demonstrating the contribution of aldosterone to cardiovascular mortality, vascular dysfunction, and renal injury in the context of advances in our understanding of the molecular biology of aldosterone.
  
  
  RESULTS
  Mineralocorticoid receptor antagonism reduces mortality in patients with congestive heart failure and following myocardial infarction. Studies in animal models and in patients with congestive heart failure or hypertension indicate that aldosterone induces oxidative stress and impairs endothelial nitric oxide synthase through a mineralocorticoid receptor-dependent mechanism. Furthermore, aldosterone can cause vasoconstriction and vasodilation through rapid nongenomic mechanisms. The contribution of the nongenomic effects of aldosterone to vascular tone may depend on underlying endothelial function. In the heart and kidney, aldosterone stimulates oxidative stress and increases expression of inflammatory markers leading to fibrosis. The induction of inflammation and fibrosis appears to be both sodium and mineralocorticoid receptor dependent. The mechanisms underlying the progression from inflammation to fibrosis remain to be elucidated. Studies measuring circulating markers of collagen turnover suggest that mineralocorticoid antagonism reduces extracellular matrix turnover and cardiac remodeling in humans as well. Similarly, mineralocorticoid receptor antagonism reduces urinary albumen excretion in clinical trials in humans.
  
  
  CONCLUSIONS
  Aldosterone induces oxidative stress, endothelial dysfunction, inflammation and fibrosis in the vasculature, heart and kidney. While most of these effects appear to be mediated via the mineralocorticoid receptor, better understanding of the mineralocorticoid receptor-independent effects of aldosterone, the role of nonaldosterone mineralocorticoid receptor agonists, and the mechanisms involved in the progression from inflammation to fibrosis and remodeling would enable the development of new strategies to slow the progression of cardiovascular and renal disease.
authors.affiliation: Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6602, USA. nancy.j.brown@vanderbilt.edu
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
mesh_terms: D000450:Aldosterone / Q000009:adverse effects* / Q000502:physiology; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology; D005355:Fibrosis / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000503:physiopathology; D000451:Mineralocorticoid Receptor Antagonists; D023421:Models, Animal; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress; D018161:Receptors, Mineralocorticoid / Q000819:agonists
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D009569:Nitric Oxide; D000450:Aldosterone