Seminars in Nephrology
Volume 27, Issue 5 , Pages 529-537 , September 2007

The Association of Aldosterone With Obesity-Related Hypertension and the Metabolic Syndrome

  • Bruno Vogt, MD

      Affiliations

    • Department of Medecine, Service of Nephrology and Hypertension, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
    • Corresponding Author InformationAddress reprint requests to Bruno Vogt, Department of Medecine, Service of Nephrology and Hypertension, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
  • ,
  • Murielle Bochud, MD

      Affiliations

    • University Institute for Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
  • ,
  • Michel Burnier, MD

      Affiliations

    • Department of Medecine, Service of Nephrology and Hypertension, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

References 

  1. Antic V, Dulloo A, Montani JP. Multiple mechanisms involved in obesity-induced hypertension. Heart Lung Circ. 2003;12:84–93
  2. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005;365:1415–1428
  3. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112:2735–2752
  4. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome—a new worldwide definition. Lancet. 2005;366:1059–1062
  5. Must A, Spadano J, Coakley EH, et al. The disease burden associated with overweight and obesity. JAMA. 1999;282:1523–1529
  6. Jones DW, Kim JS, Andrew ME, et al. Body mass index and blood pressure in Korean men and women: the Korean National Blood Pressure Survey. J Hypertens. 1994;12:1433–1437
  7. Rocchini AP, Moorehead CP, DeRemer S, et al. Pathogenesis of weight-related changes in blood pressure in dogs. Hypertension. 1989;13:922–928
  8. Goodfriend TL, Egan BM, Kelley DE. Aldosterone in obesity. Endocr Res. 1998;24:789–796
  9. Engeli S, Bohnke J, Gorzelniak K, et al. Weight loss and the renin-angiotensin-aldosterone system. Hypertension. 2005;45:356–362
  10. Tuck ML, Sowers J, Dornfeld L, et al. The effect of weight reduction on blood pressure, plasma renin activity, and plasma aldosterone levels in obese patients. N Engl J Med. 1981;304:930–933
  11. Neter JE, Stam BE, Kok FJ, et al. Influence of weight reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2003;42:878–884
  12. Garrison RJ, Kannel WB, Stokes J, et al. Incidence and precursors of hypertension in young adults: the Framingham Offspring Study. Prev Med. 1987;16:235–251
  13. McTigue K, Larson JC, Valoski A, et al. Mortality and cardiac and vascular outcomes in extremely obese women. JAMA. 2006;296:79–86
  14. Mancia G, Bousquet P, Elghozi JL, et al. The sympathetic nervous system and the metabolic syndrome. J Hypertens. 2007;25:909–920
  15. Reaven GM, Lithell H, Landsberg L. Hypertension and associated metabolic abnormalities—the role of insulin resistance and the sympathoadrenal system. N Engl J Med. 1996;334:374–381
  16. Peppard PE, Young T, Palta M, et al. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342:1378–1384
  17. Young T, Peppard P, Palta M, et al. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med. 1997;157:1746–1752
  18. Hla KM, Young TB, Bidwell T, et al. Sleep apnea and hypertension (A population-based study). Ann Intern Med. 1994;120:382–388
  19. Hall JE. The kidney, hypertension, and obesity. Hypertension. 2003;41:625–633
  20. Goodfriend TL, Calhoun DA. Resistant hypertension, obesity, sleep apnea, and aldosterone: theory and therapy. Hypertension. 2004;43:518–524
  21. Rocchini AP. Obesity hypertension. Am J Hypertens. 2002;15:50S–52S
  22. Sarafidis PA, Bakris GL. Non-esterified fatty acids and blood pressure elevation: a mechanism for hypertension in subjects with obesity/insulin resistance?. J Hum Hypertens. 2007;21:12–19
  23. Davy KP, Hall JE. Obesity and hypertension: two epidemics or one?. Am J Physiol. 2004;286:R803–R813
  24. Rahmouni K, Correia ML, Haynes WG, et al. Obesity-associated hypertension: new insights into mechanisms. Hypertension. 2005;45:9–14
  25. Burnier M. Spotlight on renin (The renin-angiotensin-aldosterone system and metabolic syndrome). J Renin Angiotensin Aldosterone Syst. 2006;7:184
  26. Egan BM, Stepniakowski K, Goodfriend TL. Renin and aldosterone are higher and the hyperinsulinemic effect of salt restriction greater in subjects with risk factors clustering. Am J Hypertens. 1994;7:886–893
  27. Bochud M, Nussberger J, Bovet P, et al. Plasma aldosterone is independently associated with the metabolic syndrome. Hypertension. 2006;48:239–245
  28. Engeli S, Negrel R, Sharma AM. Physiology and pathophysiology of the adipose tissue renin-angiotensin system. Hypertension. 2000;35:1270–1277
  29. Massiera F, Seydoux J, Geloen A, et al. Angiotensinogen-deficient mice exhibit impairment of diet-induced weight gain with alteration in adipose tissue development and increased locomotor activity. Endocrinology. 2001;142:5220–5225
  30. Gorzelniak K, Engeli S, Janke J, et al. Hormonal regulation of the human adipose-tissue renin-angiotensin system: relationship to obesity and hypertension. J Hypertens. 2002;20:965–973
  31. Janke J, Engeli S, Gorzelniak K, et al. Adipose tissue and circulating endothelial cell specific molecule-1 in human obesity. Horm Metab Res. 2006;38:28–33
  32. Harte A, McTernan P, Chetty R, et al. Insulin-mediated upregulation of the renin angiotensin system in human subcutaneous adipocytes is reduced by rosiglitazone. Circulation. 2005;111:1954–1961
  33. Harte AL, McTernan PG, McTernan CL, et al. Insulin increases angiotensinogen expression in human abdominal subcutaneous adipocytes. Diabetes Obes Metab. 2003;5:462–467
  34. Janke J, Schupp M, Engeli S, et al. Angiotensin type 1 receptor antagonists induce human in-vitro adipogenesis through peroxisome proliferator-activated receptor-gamma activation. J Hypertens. 2006;24:1809–1816
  35. Tomlinson JW, Stewart PM. Mechanisms of disease: selective inhibition of 11beta-hydroxysteroid dehydrogenase type 1 as a novel treatment for the metabolic syndrome. Nat Clin Pract Endocrinol Metab. 2005;1:92–99
  36. Mariniello B, Ronconi V, Rilli S, et al. Adipose tissue 11beta-hydroxysteroid dehydrogenase type 1 expression in obesity and Cushing’s syndrome. Eur J Endocrinol. 2006;155:435–441
  37. Jensen MD, Haymond MW, Rizza RA, et al. Influence of body fat distribution on free fatty acid metabolism in obesity. J Clin Invest. 1989;83:1168–1173
  38. Martin ML, Jensen MD. Effects of body fat distribution on regional lipolysis in obesity. J Clin Invest. 1991;88:609–613
  39. Grekin RJ, Vollmer AP, Sider RS. Pressor effects of portal venous oleate infusion (A proposed mechanism for obesity hypertension). Hypertension. 1995;26:193–198
  40. Stojiljkovic MP, Zhang D, Lopes HF, et al. Hemodynamic effects of lipids in humans. Am J Physiol. 2001;280:R1674–R1679
  41. Lopes HF, Stojiljkovic MP, Zhang D, et al. Moderate sodium restriction enhances the pressor response to hyperlipidemia in obese, hypertensive patients. J Clin Hypertens. 2002;4:173–180
  42. Goodfriend TL, Ball DL, Gardner HW. An oxidized derivative of linoleic acid affects aldosterone secretion by adrenal cells in vitro. Prostaglandins Leukot Essent Fatty Acids. 2002;67:163–167
  43. Goodfriend TL, Ball DL, Egan BM, et al. Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion. Hypertension. 2004;43:358–363
  44. Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A, et al. Human adipocytes secrete mineralocorticoid-releasing factors. Proc Natl Acad Sci U S A. 2003;100:14211–14216
  45. Nagase M, Yoshida S, Shibata S, et al. Enhanced aldosterone signaling in the early nephropathy of rats with metabolic syndrome: possible contribution of fat-derived factors. J Am Soc Nephrol. 2006;17:3438–3446
  46. Epstein M. Resistant hypertension: prevalence and evolving concepts. J Clin Hypertens. 2007;9:2–6
  47. Wolk R, Somers VK. Obesity-related cardiovascular disease: implications of obstructive sleep apnea. Diabetes Obes Metab. 2006;8:250–260
  48. Rocchini AP, Katch VL, Grekin R, et al. Role for aldosterone in blood pressure regulation of obese adolescents. Am J Cardiol. 1986;57:613–618
  49. Gordon RD, Stowasser M, Tunny TJ, et al. High incidence of primary aldosteronism in 199 patients referred with hypertension. Clin Exp Pharmacol Physiol. 1994;21:315–318
  50. Lim PO, Rodgers P, Cardale K, et al. Potentially high prevalence of primary aldosteronism in a primary-care population. Lancet. 1999;353:40
  51. Lim PO, Dow E, Brennan G, et al. High prevalence of primary aldosteronism in the Tayside hypertension clinic population. J Hum Hypertens. 2000;14:311–315
  52. Fardella CE, Mosso L, Gomez-Sanchez C, et al. Primary hyperaldosteronism in essential hypertensives: prevalence, biochemical profile, and molecular biology. J Clin Endocrinol Metab. 2000;85:1863–1867
  53. Mosso L, Carvajal C, Gonzalez A, et al. Primary aldosteronism and hypertensive disease. Hypertension. 2003;42:161–165
  54. Calhoun DA, Nishizaka MK, Zaman MA, et al. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension. 2002;40:892–896
  55. Gallay BJ, Ahmad S, Xu L, et al. Screening for primary aldosteronism without discontinuing hypertensive medications: plasma aldosterone-renin ratio. Am J Kidney Dis. 2001;37:699–705
  56. Fallo F, Veglio F, Bertello C, et al. Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. J Clin Endocrinol Metab. 2006;91:454–459
  57. Pratt-Ubunama MN, Nishizaka MK, Boedefeld RL, et al. Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension. Chest. 2007;131:453–459
  58. Logan AG, Perlikowski SM, Mente A, et al. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens. 2001;19:2271–2277
  59. Calhoun DA, Nishizaka MK, Zaman MA, et al. Aldosterone excretion among subjects with resistant hypertension and symptoms of sleep apnea. Chest. 2004;125:112–117
  60. Sartori M, Calo LA, Mascagna V, et al. Aldosterone and refractory hypertension: a prospective cohort study. Am J Hypertens. 2006;19:373–380
  61. Nishizaka MK, Zaman MA, Calhoun DA. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am J Hypertens. 2003;16:925–930
  62. Ouzan J, Perault C, Lincoff AM, et al. The role of spironolactone in the treatment of patients with refractory hypertension. Am J Hypertens. 2002;15:333–339
  63. Yamashita R, Kikuchi T, Mori Y, et al. Aldosterone stimulates gene expression of hepatic gluconeogenic enzymes through the glucocorticoid receptor in a manner independent of the protein kinase B cascade. Endocr J. 2004;51:243–251
  64. Campion J, Maestro B, Molero S, et al. Aldosterone impairs insulin responsiveness in U-937 human promonocytic cells via the downregulation of its own receptor. Cell Biochem Funct. 2002;20:237–245
  65. Giacchetti G, Ronconi V, Turchi F, et al. Aldosterone as a key mediator of the cardiometabolic syndrome in primary aldosteronism: an observational study. J Hypertens. 2007;25:177–186
  66. Widimsky J, Sindelka G, Haas T, et al. Impaired insulin action in primary hyperaldosteronism. Physiol Res. 2000;49:241–244
  67. Strauch B, Widimsky J, Sindelka G, et al. Does the treatment of primary hyperaldosteronism influence glucose tolerance?. Physiol Res. 2003;52:503–506
  68. Widimsky J, Strauch B, Sindelka G, et al. Can primary hyperaldosteronism be considered as a specific form of diabetes mellitus?. Physiol Res. 2001;50:603–607
  69. Andronico G, Cottone S, Mangano MT, et al. Insulin, renin-aldosterone system and blood pressure in obese people. Int J Obes Relat Metab Disord. 2001;25:239–242
  70. Goodfriend TL, Egan B, Stepniakowski K, et al. Relationships among plasma aldosterone, high-density lipoprotein cholesterol, and insulin in humans. Hypertension. 1995;25:30–36
  71. Kidambi S, Kotchen JM, Grim CE, et al. Association of adrenal steroids with hypertension and the metabolic syndrome in blacks. Hypertension. 2007;49:704–711
  72. Sindelka G, Widimsky J, Haas T, et al. Insulin action in primary hyperaldosteronism before and after surgical or pharmacological treatment. Exp Clin Endocrinol Diabetes. 2000;108:21–25
  73. Liu G, Grifman M, Keily B, et al. Mineralocorticoid receptor is involved in the regulation of genes responsible for hepatic glucose production. Biochem Biophys Res Commun. 2006;342:1291–1296
  74. Goodfriend TL, Egan BM, Kelley DE. Plasma aldosterone, plasma lipoproteins, obesity and insulin resistance in humans. Prostaglandins Leukot Essent Fatty Acids. 1999;60:401–405
  75. Lind L, Lithell H, Wide L, et al. Metabolic cardiovascular risk factors and the renin-aldosterone system in essential hypertension. J Hum Hypertens. 1992;6:27–29
  76. Oelkers W, Foidart JM, Dombrovicz N, et al. Effects of a new oral contraceptive containing an antimineralocorticoid progestogen, drospirenone, on the renin-aldosterone system, body weight, blood pressure, glucose tolerance, and lipid metabolism. J Clin Endocrinol Metab. 1995;80:1816–1821
  77. White WB, Hanes V, Chauhan V, et al. Effects of a new hormone therapy, drospirenone and 17-beta-estradiol, in postmenopausal women with hypertension. Hypertension. 2006;48:246–253
  78. Tanko LB, Christiansen C. Effects of 17beta-oestradiol plus different doses of drospirenone on adipose tissue, adiponectin and atherogenic metabolites in postmenopausal women. J Intern Med. 2005;258:544–553
  79. Gaudio G, Guasti L, Schizzarotto A, et al. Changes in plasma lipids during renin-angiotensin system blockade by combination therapy (enalapril plus valsartan) in patients with diabetes and hypertension. J Cardiovasc Pharmacol. 2005;45:362–366
  80. Takai S, Jin D, Muramatsu M, et al. Eplerenone inhibits atherosclerosis in nonhuman primates. Hypertension. 2005;46:1135–1139
  81. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure (Randomized Aldactone Evaluation Study Investigators). N Engl J Med. 1999;341:709–717
  82. Pitt B, White H, Nicolau J, et al. Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. J Am Coll Cardiol. 2005;46:425–431
  83. Egan BM, Papademetriou V, Wofford M, et al. Metabolic syndrome and insulin resistance in the TROPHY sub-study: contrasting views in patients with high-normal blood pressure. Am J Hypertens. 2005;18:3–12
  84. Russo P, Lauria F, Loguercio M, et al. −344C/T Variant in the promoter of the aldosterone synthase gene (CYP11B2) is associated with metabolic syndrome in men. Am J Hypertens. 2007;20:218–222
  85. de Paula RB, da Silva AA, Hall JE. Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration. Hypertension. 2004;43:41–47
  86. Engeli S, Schling P, Gorzelniak K, et al. The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome?. Int J Biochem Cell Biol. 2003;35:807–825

PII: S0270-9295(07)00094-0

doi: 10.1016/j.semnephrol.2007.07.009

Seminars in Nephrology
Volume 27, Issue 5 , Pages 529-537 , September 2007