James R. Sowers, MD; Adam Whaley-Connell, DO; Murray Epstein, MD
Acknowledgment: The authors thank Amanda Yarberry Behr, MA, CMI, for her excellent assistance with the artwork and Brenda Hunter for expert preparation of this manuscript.
Grant Support: By the National Institutes of Health (grant R01 HL73101-01A1 NIH/NHLBI) and the Department of Veterans Affairs (Merit Review) (Dr. Sowers); the Department of Veterans Affairs VISN-15, National Kidney Foundation, and the Missouri Kidney Program (Dr. Whaley-Connell) and the South Florida Veterans Affairs Foundation for Research and Education (Dr. Epstein).
Potential Financial Conflicts of Interest:Grants received: M. Epstein (Pfizer).
Requests for Single Reprints: Murray Epstein, MD, University of Miami School of Medicine, Nephrology Section, Veterans Affairs Medical Center, 1201 Northwest 16th Street, Miami, FL 33125; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Sowers: University of Missouri, D109 HSC, Columbia, MO 65212.
Dr. Whaley-Connell: University of Missouri, CE417, 5 Hospital Drive, Columbia, MO 65212.
Dr. Epstein: University of Miami School of Medicine, Nephrology Section, Veterans Affairs Medical Center, 1201 Northwest 16th Street, Miami, FL 33125.
Sowers JR, Whaley-Connell A, Epstein M. Narrative Review: The Emerging Clinical Implications of the Role of Aldosterone in the Metabolic Syndrome and Resistant Hypertension. Ann Intern Med. 2009;150:776-783. doi: 10.7326/0003-4819-150-11-200906020-00005
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Published: Ann Intern Med. 2009;150(11):776-783.
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 reninâ€“angiotensinâ€“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 Î²-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.
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Cardiology, Nephrology, Hypertension, Obesity, Coronary Risk Factors.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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