title: Narrative review: the emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension.
abstract: The prevalence of obesity, diabetes, hypertension, and cardiovascular and chronic kidney disease is increasing in developed countries. Obesity, insulin resistance, and hypertension commonly cluster with other risk factors for cardiovascular and chronic kidney disease to form the metabolic syndrome. Emerging evidence supports a paradigm shift in our understanding of the renin-angiotensin-aldosterone system and in aldosterone's ability to promote insulin resistance and participate in the pathogenesis of the metabolic syndrome and resistant hypertension. Recent data suggest that excess circulating aldosterone promotes the development of both disorders by impairing insulin metabolic signaling and endothelial function, which in turn leads to insulin resistance and cardiovascular and renal structural and functional abnormalities. Indeed, hyperaldosteronism is associated with impaired pancreatic beta-cell function, skeletal muscle insulin sensitivity, and elevated production of proinflammatory adipokines from adipose tissue, which results in systemic inflammation and impaired glucose tolerance. Accumulating evidence indicates that the cardiovascular and renal abnormalities associated with insulin resistance are mediated in part by aldosterone acting on the mineralocorticoid receptor. Although we have known that mineralocorticoid receptor blockade attenuates cardiovascular and renal injury, only recently have we learned that mineralocorticoid receptor blockade improves pancreatic insulin release, insulin-mediated glucose utilization, and endothelium-dependent vasorelaxation. In summary, aldosterone excess has detrimental metabolic effects that contribute to the metabolic syndrome and endothelial dysfunction, which in turn contribute to the development of resistant hypertension as well as cardiovascular disease and chronic kidney disease.
authors.affiliation: University of Missouri, Columbia, Missouri, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Sowers
authors.forename: Adam
authors.initials: A
authors.lastname: Whaley-Connell
authors.forename: Murray
authors.initials: M
authors.lastname: Epstein
mesh_terms: D000450:Aldosterone / Q000097:blood / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D007333:Insulin Resistance; D007674:Kidney Diseases / Q000503:physiopathology; D024821:Metabolic Syndrome / Q000097:blood / Q000503:physiopathology*; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D000450:Aldosterone