Narrative Review: The Emerging Clinical Implications of the Role of Aldosterone in the Metabolic Syndrome and Resistant Hypertension
Open accessAbstract
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.
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In vitro and rodent studies show that aldosterone-induced mineralocorticoid activation impairs insulin sensitivity in adipocytes and skeletal muscle.
“In vitro and rodent studies show that aldosterone-induced mineralocorticoid activation impairs insulin sensitivity in adipocytes and skeletal muscle [40,41].”
From Insulin sensitivity and pancreatic β-cell function in patients with primary aldosteronism (2021) · cites this paper as [40]
In “Aldosterone Interactions With Adipose Tissue” (page unavailable), the review reports impaired insulin-induced glucose uptake in rodent fat tissue. “Aldosterone Effects on Systemic Insulin Metabolic Signaling” (page unavailable) reports improved skeletal-muscle glucose uptake after mineralocorticoid-receptor blockade in a rodent model. These passages support the rodent evidence, but our copy does not establish the claimed in vitro evidence for impaired insulin sensitivity in adipocytes and skeletal muscle. (LLM, conf=0.82)
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- Authors
- Sowers, J. R., Whaley-Connell, A., & Epstein, M.
- Affiliations
- University of Miami (US)
- Corresponding author
- Sowers, James R.
- ORCID
- Sowers, James R.
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2009-06-02
- Volume
- 150
- Issue
- 11
- Pages
- 776-783
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- PMC
- PMC2824330
- OpenAlex
- W2130687169
- Cited by
- 351
- References
- 59
- Citations by year
- 2026: 4 · 2025: 6 · 2023: 13 · 2022: 9 · 2021: 14 · 2020: 10 · 2019: 11 · 2018: 18 · 2017: 18 · 2016: 14 · 2015: 20 · 2014: 33 · 2013: 36 · 2012: 49
- FWCI
- 6.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01 HL73101‑01A1, R01HL073101)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- aldosterone, metabolic syndrome, resistant hypertension, renin-angiotensin-aldosterone system, insulin resistance, mineralocorticoid receptor blockade, endothelial dysfunction, hyperaldosteronism, cardiovascular disease, chronic kidney disease, adipokines, systemic inflammation, beta-cell function, skeletal muscle insulin sensitivity
- MeSH terms
- Aldosterone, Mineralocorticoid Receptor Antagonists, Cardiovascular Diseases, Endothelium, Vascular, Humans, Hypertension, Insulin Resistance, Kidney Diseases, Renin-Angiotensin System, Metabolic Syndrome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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