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  • Review Article
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Aldosterone and arterial hypertension

Abstract

In the setting of primary aldosteronism, elevated aldosterone levels are associated with increased blood pressure. Aldosterone concentrations within the normal range, however, can also alter blood pressure. Furthermore, the aldosterone-to-renin ratio, an indicator of aldosterone excess, is associated with hypertension, even in patients without excessive absolute aldosterone levels. In this Review we assess the data on the role of aldosterone in the development and maintenance of hypertension. We provide an overview of the complex crosstalk between genetic and environmental factors, and about aldosterone-mediated arterial hypertension and target organ damage. The discussion is organized according to major targets of aldosterone action: the collecting duct in the kidney, the vasculature and the central nervous system. The antihypertensive efficacy of mineralocorticoid-receptor blockers, even in patients with aldosterone values in the normal range, supports the evidence that aldosterone plays a part in blood pressure elevation in the absence of primary aldosteronism.

Key Points

  • Clinical and experimental evidence shows that aldosterone makes a major contribution beyond primary aldosteronism to the pathogenesis of arterial hypertension

  • Aldosterone excess contributes to endothelial dysfunction, inflammation and vascular remodeling, which result in the development and maintenance of arterial hypertension, via genomic and nongenomic pathways

  • Aldosterone-mediated effects on epithelial and nonepithelial tissues depend on mineralocorticoid sensitivity, which is modulated by salt and angiotensin II

  • Renal Na+ and fluid retention, endothelial dysfunction, increased peripheral resistance and central sympathetic drive are major pathogenic pathways of aldosterone-induced arterial hypertension

  • Mineralocorticoid-receptor blockers are useful drugs to treat aldosterone-mediated arterial hypertension, especially when other antihypertensive drugs insufficiently control blood pressure

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Figure 1: The renin–angiotensin–aldosterone system.
Figure 2: Mechanisms of aldosterone-mediated arterial hypertension.

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References

  1. WHO. World Health Report 2002: reducing risks, promoting healthy life (WHO, Geneva, 2002).

  2. Calhoun, D. A. et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation 117, e510–e526 (2008).

    Article  PubMed  Google Scholar 

  3. Bramlage, P. et al. Hypertension in overweight and obese primary care patients is highly prevalent and poorly controlled. Am. J. Hypertens. 17, 904–910 (2004).

    Article  PubMed  Google Scholar 

  4. Perkovic, V., Huxley, R., Wu, Y., Prabhakaran, D. & MacMahon, S. The burden of blood pressure-related disease: a neglected priority for global health. Hypertension 50, 991–997 (2007).

    Article  CAS  PubMed  Google Scholar 

  5. Sarafidis, P. A. & Bakris, G. L. Resistant hypertension: an overview of evaluation and treatment. J. Am. Coll. Cardiol. 52, 1749–1757 (2008).

    Article  PubMed  Google Scholar 

  6. Vasan, R. S. et al. Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N. Engl. J. Med. 351, 33–41 (2004).

    Article  CAS  PubMed  Google Scholar 

  7. Ingelsson, E. et al. Multimarker approach to evaluate the incidence of the metabolic syndrome and longitudinal changes in metabolic risk factors: the Framingham Offspring Study. Circulation 116, 984–992 (2007).

    Article  CAS  PubMed  Google Scholar 

  8. Kappert, K. & Unger, T. Role of the renin-angiotensin system in hypertension. Hot Topics in Hypertension [online], (2008).

  9. Pratt, J. H. Central role for ENaC in development of hypertension. J. Am. Soc. Nephrol. 16, 3154–3159 (2005).

    Article  CAS  PubMed  Google Scholar 

  10. Connell, J. M., MacKenzie, S. M., Freel, E. M., Fraser, R. & Davies, E. A lifetime of aldosterone excess: long-term consequences of altered regulation of aldosterone production for cardiovascular function. Endocr. Rev. 29, 133–154 (2008).

    Article  CAS  PubMed  Google Scholar 

  11. Ehrhart-Bornstein, M. et al. Human adipocytes secrete mineralocorticoid-releasing factors. Proc. Natl Acad. Sci. USA 100, 14211–14216 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Oelkers, W. et al. Sensitization of the adrenal cortex to angiotensin II in sodium-deplete man. Circ. Res. 40, 69–77 (1974).

    Article  Google Scholar 

  13. Schlaich, M. P., Schobel, H. P., Hilgers, K. & Schmieder, R. E. Impact of aldosterone on left ventricular structure and function in young normotensive and mildly hypertensive subjects. Am. J. Cardiol. 85, 1199–1206 (2000).

    Article  CAS  PubMed  Google Scholar 

  14. Intersalt Cooperative Research Group. Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. BMJ 297, 319–328 (1988).

  15. Stamler, J. et al. INTERMAP: background, aims, design, methods, and descriptive statistics (nondietary). J. Hum. Hypertens. 17, 591–608 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mohan, S. & Campbell, N. R. Salt and high blood pressure. Clin. Sci. (Lond.) 117, 1–11 (2009).

    Article  CAS  Google Scholar 

  17. Meland, E. & Aamland, A. Salt restriction among hypertensive patients: modest blood pressure effect and no adverse effects. Scand. J. Prim. Health Care 27, 97–103 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Arriza, J. L. et al. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science 237, 268–275 (1987).

    Article  CAS  PubMed  Google Scholar 

  19. Funder, J. W. The nongenomic actions of aldosterone. Endocr. Rev. 26, 313–321 (2005).

    Article  CAS  PubMed  Google Scholar 

  20. Grossmann, C. & Gekle, M. New aspects of rapid aldosterone signaling. Mol. Cell. Endocrinol. 308, 53–62 (2009).

    Article  CAS  PubMed  Google Scholar 

  21. Lemarie, C. A., Paradis, P. & Schiffrin, E. L. New insights on signaling cascades induced by cross-talk between angiotensin II and aldosterone. J. Mol. Med. 86, 673–678 (2008).

    Article  CAS  PubMed  Google Scholar 

  22. Jaffe, I. Z. & Mendelsohn, M. E. Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circ. Res. 96, 643–650 (2005).

    Article  CAS  PubMed  Google Scholar 

  23. Montezano, A. C. & Touyz, R. M. Networking between systemic angiotensin II and cardiac mineralocorticoid receptors. Hypertension 52, 1016–1018 (2008).

    Article  CAS  PubMed  Google Scholar 

  24. Montezano, A. C. et al. Aldosterone and angiotensin II synergistically stimulate migration in vascular smooth muscle cells through c-Src-regulated redox-sensitive RhoA pathways. Arterioscler. Thromb. Vasc. Biol. 28, 1511–1518 (2008).

    Article  CAS  PubMed  Google Scholar 

  25. Harada, E. et al. Aldosterone induces angiotensin-converting-enzyme gene expression in cultured neonatal rat cardiocytes. Circulation 104, 137–139 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. Chai, W. et al. Nongenomic effects of aldosterone in the human heart: interaction with angiotensin II. Hypertension 46, 701–706 (2005).

    Article  CAS  PubMed  Google Scholar 

  27. Xiao, F., Puddefoot, J. R., Barker, S. & Vinson, G. P. Mechanism for aldosterone potentiation of angiotensin II-stimulated rat arterial smooth muscle cell proliferation. Hypertension 44, 340–345 (2004).

    Article  CAS  PubMed  Google Scholar 

  28. Grossmann, C. et al. Aldosterone-induced EGFR expression: interaction between the human mineralocorticoid receptor and the human EGFR promoter. Am. J. Physiol. Endocrinol. Metab. 292, E1790–E1800 (2007).

    Article  CAS  PubMed  Google Scholar 

  29. Ying, W. Z. & Sanders, P. W. Enhanced expression of EGF receptor in a model of salt-sensitive hypertension. Am. J. Physiol. Renal Physiol. 289, F314–F321 (2005).

    Article  CAS  PubMed  Google Scholar 

  30. Min, L. J. et al. Aldosterone and angiotensin II synergistically induce mitogenic response in vascular smooth muscle cells. Circ. Res. 97, 434–442 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. Nagase, M., Matsui, H., Shibata, S., Gotoda, T. & Fujita, T. Salt-induced nephropathy in obese spontaneously hypertensive rats via paradoxical activation of the mineralocorticoid receptor: role of oxidative stress. Hypertension 50, 877–883 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. Kitiyakara, C. et al. Salt intake, oxidative stress, and renal expression of NADPH oxidase and superoxide dismutase. J. Am. Soc. Nephrol. 14, 2775–2782 (2003).

    Article  CAS  PubMed  Google Scholar 

  33. Funder, J. W. Reconsidering the roles of the mineralocorticoid receptor. Hypertension 53, 286–290 (2009).

    CAS  PubMed  Google Scholar 

  34. Mizuno, Y. et al. Aldosterone production is activated in failing ventricle in humans. Circulation 103, 72–77 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Nishikawa, T. et al. Human renal mesangial cells produce aldosterone in response to low-density lipoprotein (LDL). J. Steroid Biochem. Mol. Biol. 96, 309–316 (2005).

    Article  CAS  PubMed  Google Scholar 

  36. He, F. J. & MacGregor, G. A. A comprehensive review on salt and health and current experience of worldwide salt reduction programmes. J. Hum. Hypertens. 23, 363–384 (2009).

    Article  CAS  PubMed  Google Scholar 

  37. Nowaczynski, W., Oliver, W. J. & Neel, J. V. Serum aldosterone and protein-binding variables in Yanomama Indians: a no-salt culture as compared to partially acculturated Guaymi Indians. Clin. Physiol. Biochem. 3, 289–306 (1985).

    CAS  PubMed  Google Scholar 

  38. Guyton, A. C. Kidneys and fluids in pressure regulation. Small volume but large pressure changes. Hypertension 19 (Suppl.), I2–I8 (1992).

    Article  CAS  PubMed  Google Scholar 

  39. Machnik, A. et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat. Med. 15, 545–552 (2009).

    Article  CAS  PubMed  Google Scholar 

  40. Schiffrin, E. L. Effects of aldosterone on the vasculature. Hypertension 47, 312–318 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Cooper, S. A. et al. Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance. Am. J. Physiol. Heart Circ. Physiol. 293, H2009–H2023 (2007).

    Article  CAS  PubMed  Google Scholar 

  42. Skott, O. et al. Rapid actions of aldosterone in vascular health and disease—friend or foe? Pharmacol. Ther. 111, 495–507 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Gekle, M. & Grossmann, C. Actions of aldosterone in the cardiovascular system: the good, the bad, and the ugly? Pflugers Arch. 458, 231–246 (2009).

    Article  CAS  PubMed  Google Scholar 

  44. Arima, S. et al. Nongenomic vascular action of aldosterone in the glomerular microcirculation. J. Am. Soc. Nephrol. 14, 2255–2263 (2003).

    Article  CAS  PubMed  Google Scholar 

  45. Nishizaka, M. K., Zaman, M. A., Green, S. A., Renfroe, K. Y. & Calhoun, D. A. Impaired endothelium-dependent flow-mediated vasodilation in hypertensive subjects with hyperaldosteronism. Circulation 109, 2857–2861 (2004).

    Article  CAS  PubMed  Google Scholar 

  46. Ahmad, N., Romero, D. G., Gomez-Sanchez, E. P. & Gomez-Sanchez, C. E. Do human vascular endothelial cells produce aldosterone? Endocrinology 145, 3626–3629 (2004).

    Article  CAS  PubMed  Google Scholar 

  47. Oberleithner, H. et al. Plasma sodium stiffens vascular endothelium and reduces nitric oxide release. Proc. Natl Acad. Sci. USA 104, 16281–16286 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Oberleithner, H., Riethmuller, C., Ludwig, T., Hausberg, M. & Schillers, H. Aldosterone remodels human endothelium. Acta Physiol. (Oxf.) 187, 305–312 (2006).

    Article  CAS  Google Scholar 

  49. Brown, N. J. Aldosterone and vascular inflammation. Hypertension 51, 161–167 (2008).

    Article  CAS  PubMed  Google Scholar 

  50. Ma, L. J. & Fogo, A. B. PAI-1 and kidney fibrosis. Front. Biosci. 14, 2028–2041 (2009).

    Article  CAS  Google Scholar 

  51. Rocha, R. et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am. J. Physiol. Heart Circ. Physiol. 283, H1802–H1810 (2002).

    Article  CAS  PubMed  Google Scholar 

  52. Blasi, E. R. et al. Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int. 63, 1791–1800 (2003).

    Article  CAS  PubMed  Google Scholar 

  53. Kotchen, T. A., Kotchen, J. M., Grim, C. E., Krishnaswami, S. & Kidambi, S. Aldosterone and alterations of hypertension-related vascular function in African Americans. Am. J. Hypertens. 22, 319–324 (2009).

    Article  CAS  PubMed  Google Scholar 

  54. Jaffe, I. Z., Tintut, Y., Newfell, B. G., Demer, L. L. & Mendelsohn, M. E. Mineralocorticoid receptor activation promotes vascular cell calcification. Arterioscler. Thromb. Vasc. Biol. 27, 799–805 (2007).

    Article  CAS  PubMed  Google Scholar 

  55. Gomez-Sanchez, C. E. et al. Aldosterone biosynthesis in the rat brain. Endocrinology 138, 3369–3373 (1997).

    Article  CAS  PubMed  Google Scholar 

  56. Geerling, J. C. & Loewy, A. D. Aldosterone in the brain. Am. J. Physiol. Renal Physiol. 297, F559–F576 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Huang, B. S., Wang, H. & Leenen, F. H. Chronic central infusion of aldosterone leads to sympathetic hyperreactivity and hypertension in Dahl S but not Dahl R rats. Am. J. Physiol. Heart Circ. Physiol. 288, H517–H524 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Minoura, Y., Onimaru, H., Iigaya, K., Homma, I. & Kobayashi, Y. Eectrophysiologic responses of sympathetic preganglionic neurons to angiotensin II and aldosterone. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297, R699–R706 (2009).

    Article  CAS  PubMed  Google Scholar 

  59. Huang, B. S. et al. Activation of brain renin-angiotensin-aldosterone system by central sodium in Wistar rats. Am. J. Physiol. Heart Circ. Physiol. 291, H1109–H1117 (2006).

    Article  CAS  PubMed  Google Scholar 

  60. Huang, B. S., White, R. A., Jeng, A. Y. & Leenen, F. H. Role of central nervous system aldosterone synthase and mineralocorticoid receptors in salt-induced hypertension in Dahl salt-sensitive rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296, R994–R1000 (2009).

    Article  CAS  PubMed  Google Scholar 

  61. Ye, P. et al. Regulation of aldosterone synthase gene expression in the rat adrenal gland and central nervous system by sodium and angiotensin II. Endocrinology 144, 3321–3328 (2003).

    Article  CAS  PubMed  Google Scholar 

  62. Sakai, R. R., McEwen, B. S., Fluharty, S. J. & Ma, L. Y. The amygdala: site of genomic and nongenomic arousal of aldosterone-induced sodium intake. Kidney Int. 57, 1337–1345 (2000).

    Article  CAS  PubMed  Google Scholar 

  63. Ganong, W. F. Circumventricular organs: definition and role in the regulation of endocrine and autonomic function. Clin. Exp. Pharmacol. Physiol. 27, 422–427 (2000).

    Article  CAS  PubMed  Google Scholar 

  64. Francis, J. et al. Central mineralocorticoid receptor blockade improves volume regulation and reduces sympathetic drive in heart failure. Am. J. Physiol. Heart Circ. Physiol. 281, H2241–H2251 (2001).

    Article  CAS  PubMed  Google Scholar 

  65. Geerling, J. C., Engeland, W. C., Kawata, M. & Loewy, A. D. Aldosterone target neurons in the nucleus tractus solitarius drive sodium appetite. J. Neurosci. 26, 411–417 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Reynolds, R. M. et al. Programming of hypertension: associations of plasma aldosterone in adult men and women with birthweight, cortisol, and blood pressure. Hypertension 53, 932–936 (2009).

    Article  CAS  PubMed  Google Scholar 

  67. Isaji, M. et al. Correlation between left ventricular mass and urinary sodium excretion in specific genotypes of CYP11B2. J. Hypertens. 23, 1149–1157 (2005).

    Article  CAS  PubMed  Google Scholar 

  68. Lim, P. O. et al. Variation at the aldosterone synthase (CYP11B2) locus contributes to hypertension in subjects with a raised aldosterone-to-renin ratio. J. Clin. Endocrinol. Metab. 87, 4398–4402 (2002).

    Article  CAS  PubMed  Google Scholar 

  69. Tsujita, Y. et al. Lack of association between genetic polymorphism of CYP11B2 and hypertension in Japanese: the Suita Study. Hypertens. Res. 24, 105–109 (2001).

    Article  CAS  PubMed  Google Scholar 

  70. Davies, E. et al. Aldosterone excretion rate and blood pressure in essential hypertension are related to polymorphic differences in the aldosterone synthase gene CYP11B2. Hypertension 33, 703–707 (1999).

    Article  CAS  PubMed  Google Scholar 

  71. Castellano, M. et al. Genetic polymorphism of the renin-angiotensin-aldosterone system and arterial hypertension in the Italian population: the GENIPER Project. J. Hypertens. 21, 1853–1860 (2003).

    Article  CAS  PubMed  Google Scholar 

  72. Nejatizadeh, A. et al. CYP11B2 gene haplotypes independently and in concurrence with aldosterone and aldosterone to renin ratio increase the risk of hypertension. Clin. Biochem. doi:10.1016/j.clinbiochem.2009.09.015.

  73. Sookoian, S., Gianotti, T. F., Gonzalez, C. D. & Pirola, C. J. Association of the C-344T aldosterone synthase gene variant with essential hypertension: a meta-analysis. J. Hypertens. 25, 5–13 (2007).

    Article  CAS  PubMed  Google Scholar 

  74. Makhanova, N., Hagaman, J., Kim, H. S. & Smithies, O. Salt-sensitive blood pressure in mice with increased expression of aldosterone synthase. Hypertension 51, 134–140 (2008).

    Article  CAS  PubMed  Google Scholar 

  75. Schlaich, M. P. et al. Altered aldosterone response to salt intake and angiotensin II infusion in young normotensive men with parental history of arterial hypertension. J. Hypertens. 20, 117–124 (2002).

    Article  CAS  PubMed  Google Scholar 

  76. Kathiresan, S. et al. Clinical and genetic correlates of serum aldosterone in the community: the Framingham Heart Study. Am. J. Hypertens. 18, 657–665 (2005).

    Article  CAS  PubMed  Google Scholar 

  77. Kotchen, T. A. et al. Genetic determinants of hypertension: identification of candidate phenotypes. Hypertension 36, 7–13 (2000).

    Article  CAS  PubMed  Google Scholar 

  78. Inglis, G. C. et al. Familial pattern of corticosteroids and their metabolism in adult human subjects—the Scottish Adult Twin Study. J. Clin. Endocrinol. Metab. 84, 4132–4137 (1999).

    CAS  PubMed  Google Scholar 

  79. Newton-Cheh, C. et al. Clinical and genetic correlates of aldosterone-to-renin ratio and relations to blood pressure in a community sample. Hypertension 49, 846–856 (2007).

    Article  CAS  PubMed  Google Scholar 

  80. Gaddam, K. K. et al. Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion. Arch. Intern. Med. 168, 1159–1164 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Lin, L. et al. Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia. Clin. Endocrinol. (Oxf.) 66, 205–210 (2007).

    Article  CAS  Google Scholar 

  82. Luft, F. C. & Weinberger, M. H. Heterogeneous responses to changes in dietary salt intake: the salt-sensitivity paradigm. Am. J. Clin. Nutr. 65 (Suppl.), S612–S617 (1997).

    Article  Google Scholar 

  83. Hannila-Handelberg, T. et al. Common variants of the beta and gamma subunits of the epithelial sodium channel and their relation to plasma renin and aldosterone levels in essential hypertension. BMC Med. Genet. 6, 4 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Shimkets, R. A. et al. Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell 79, 407–414 (1994).

    Article  CAS  PubMed  Google Scholar 

  85. von Wowern, F. et al. Genetic variance of SGK-1 is associated with blood pressure, blood pressure change over time and strength of the insulin-diastolic blood pressure relationship. Kidney Int. 68, 2164–2172 (2005).

    Article  CAS  PubMed  Google Scholar 

  86. Kucharz, E. J. Michal Litynski—a forgotten author of the first description on primary hyperaldosteronism [Polish]. Pol. Arch. Med. Wewn. 117, 57–58 (2007).

    PubMed  Google Scholar 

  87. Conn, J. W. & Louis, L. H. Primary aldosteronism, a new clinical entity. Ann. Intern. Med. 44, 1–15 (1956).

    Article  CAS  PubMed  Google Scholar 

  88. Genest, J. et al. Human arterial hypertension: a state of mild chronic hyperaldosteronism? Science 123, 503–505 (1956).

    Article  CAS  PubMed  Google Scholar 

  89. Russell, R. P. & Masi, A. T. Significant associations of adrenal cortical abnormalities with “essential” hypertension. Am. J. Med. 54, 44–51 (1973).

    Article  CAS  PubMed  Google Scholar 

  90. Mosso, L. et al. Primary aldosteronism and hypertensive disease. Hypertension 42, 161–165 (2003).

    Article  CAS  PubMed  Google Scholar 

  91. Pilz, S. et al. Graz Endocrine Causes of Hypertension (GECOH) study: a diagnostic accuracy study of aldosterone to active renin ratio in screening for primary aldosteronism. BMC Endocr. Disord. 9, 11 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Calhoun, D. A., Nishizaka, M. K., Zaman, M. A., Thakkar, R. B. & Weissmann, P. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 40, 892–896 (2002).

    Article  CAS  PubMed  Google Scholar 

  93. Calhoun, D. A. Is there an unrecognized epidemic of primary aldosteronism? Pro. Hypertension 50, 447–453 (2007).

    Article  CAS  PubMed  Google Scholar 

  94. Kaplan, N. M. Is there an unrecognized epidemic of primary aldosteronism? Con. Hypertension 50, 454–458 (2007).

    Article  CAS  PubMed  Google Scholar 

  95. Fiquet-Kempf, B., Launay-Mignot, P., Bobrie, G. & Plouin, P. F. Is primary aldosteronism underdiagnosed in clinical practice? Clin. Exp. Pharmacol. Physiol. 28, 1083–1086 (2001).

    Article  CAS  PubMed  Google Scholar 

  96. Sartori, M. et al. Aldosterone and refractory hypertension: a prospective cohort study. Am. J. Hypertens. 19, 373–379 (2006).

    Article  CAS  PubMed  Google Scholar 

  97. Meneton, P. et al. High plasma aldosterone and low renin predict blood pressure increase and hypertension in middle-aged Caucasian populations. J. Hum. Hypertens. 22, 550–558 (2008).

    Article  CAS  PubMed  Google Scholar 

  98. Lieb, W. et al. Multimarker approach to evaluate correlates of vascular stiffness: the Framingham Heart Study. Circulation 119, 37–43 (2009).

    Article  PubMed  Google Scholar 

  99. Tomaschitz, A. et al. How does the aldosterone renin ratio impact blood pressure levels? A cross-sectional study of 3056 normo- and hypertensive patients referred to coronary angiography. Endocrine Abstracts 16, P9 (2008).

    Google Scholar 

  100. Lim, P. O., Struthers, A. D. & MacDonald, T. M. The neurohormonal natural history of essential hypertension: towards primary or tertiary aldosteronism? J. Hypertens. 20, 11–15 (2002).

    Article  CAS  PubMed  Google Scholar 

  101. Eide, I. K., Torjesen, P. A., Drolsum, A., Babovic, A. & Lilledahl, N. P. Low-renin status in therapy-resistant hypertension: a clue to efficient treatment. J. Hypertens. 22, 2217–2226 (2004).

    Article  CAS  PubMed  Google Scholar 

  102. Mulatero, P. et al. CYP11B2 gene polymorphisms in idiopathic hyperaldosteronism. Hypertension 35, 694–698 (2000).

    Article  CAS  PubMed  Google Scholar 

  103. Pratt, J. H. Low-renin hypertension: more common than we think? Cardiol. Rev. 8, 202–206 (2000).

    Article  CAS  PubMed  Google Scholar 

  104. Pimenta, E. et al. Aldosterone excess and resistance to 24-h blood pressure control. J. Hypertens. 25, 2131–2137 (2007).

    Article  CAS  PubMed  Google Scholar 

  105. Lastra-Lastra, G., Sowers, J. R., Restrepo-Erazo, K., Manrique-Acevedo, C. & Lastra-Gonzalez, G. Role of aldosterone and angiotensin II in insulin resistance: an update. Clin. Endocrinol. (Oxf.) 71, 1–6 (2009).

    Article  CAS  Google Scholar 

  106. Hitomi, H. et al. Aldosterone suppresses insulin signaling via the downregulation of insulin receptor substrate-1 in vascular smooth muscle cells. Hypertension 50, 750–755 (2007).

    Article  CAS  PubMed  Google Scholar 

  107. Mosso, L. M. et al. A possible association between primary aldosteronism and a lower beta-cell function. J. Hypertens. 25, 2125–2130 (2007).

    Article  CAS  PubMed  Google Scholar 

  108. Bochud, M. et al. Plasma aldosterone is independently associated with the metabolic syndrome. Hypertension 48, 239–245 (2006).

    Article  CAS  PubMed  Google Scholar 

  109. Goodfriend, T. L. & Calhoun, D. A. Resistant hypertension, obesity, sleep apnea, and aldosterone: theory and therapy. Hypertension 43, 518–524 (2004).

    Article  CAS  PubMed  Google Scholar 

  110. Sowers, J. R., 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. 150, 776–783 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  111. Tolagen, K. & Karlberg, B. E. Plasma and urinary aldosterone and their interrelations with blood pressure, plasma renin activity and urinary electrolytes in normotensive subjects. Scand. J. Clin. Lab. Invest. 38, 241–247 (1978).

    Article  CAS  PubMed  Google Scholar 

  112. Duprez, D. A. et al. Influence of arterial blood pressure and aldosterone on left ventricular hypertrophy in moderate essential hypertension. Am. J. Cardiol. 71, 17A–20A (1993).

    Article  CAS  PubMed  Google Scholar 

  113. Walker, W. G., Whelton, P. K., Saito, H., Russell, R. P. & Hermann, J. Relation between blood pressure and renin, renin substrate, angiotensin II, aldosterone and urinary sodium and potassium in 574 ambulatory subjects. Hypertension 1, 287–291 (1979).

    Article  CAS  PubMed  Google Scholar 

  114. Grim, C. E. et al. Hyperaldosteronism and hypertension: ethnic differences. Hypertension 45, 766–772 (2005).

    Article  CAS  PubMed  Google Scholar 

  115. Di Zhang, A. et al. Cross-talk between mineralocorticoid and angiotensin II signaling for cardiac remodeling. Hypertension 52, 1060–1067 (2008).

    Article  PubMed  CAS  Google Scholar 

  116. Virdis, A. et al. Spironolactone improves angiotensin-induced vascular changes and oxidative stress. Hypertension 40, 504–510 (2002).

    Article  CAS  PubMed  Google Scholar 

  117. Lea, W. B. et al. Aldosterone antagonism or synthase inhibition reduces end-organ damage induced by treatment with angiotensin and high salt. Kidney Int. 75, 936–944 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Fujita, T. Aldosterone in salt-sensitive hypertension and metabolic syndrome. J. Mol. Med. 86, 729–734 (2008).

    Article  CAS  PubMed  Google Scholar 

  119. Douglas, J. G., Hollifield, J. W. & Liddle, G. W. Treatment of low-renin essential hypertension. Comparison of spironolactone and a hydrochlorothiazide-triamterene combination. JAMA 227, 518–521 (1974).

    Article  CAS  PubMed  Google Scholar 

  120. Hood, S. J., Taylor, K. P., Ashby, M. J. & Brown, M. J. The spironolactone, amiloride, losartan, and thiazide (SALT) double-blind crossover trial in patients with low-renin hypertension and elevated aldosterone-renin ratio. Circulation 116, 268–275 (2007).

    Article  CAS  PubMed  Google Scholar 

  121. Nishizaka, M. K., Zaman, M. A. & Calhoun, D. A. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am. J. Hypertens. 16, 925–930 (2003).

    Article  CAS  PubMed  Google Scholar 

  122. Lane, D. A., Shah, S. & Beevers, D. G. Low-dose spironolactone in the management of resistant hypertension: a surveillance study. J. Hypertens. 25, 891–894 (2007).

    Article  CAS  PubMed  Google Scholar 

  123. Chapman, N. et al. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension 49, 839–845 (2007).

    Article  CAS  PubMed  Google Scholar 

  124. Gross, E., Rothstein, M., Dombek, S. & Juknis, H. I. Effect of spironolactone on blood pressure and the renin-angiotensin-aldosterone system in oligo-anuric hemodialysis patients. Am. J. Kidney Dis. 46, 94–101 (2005).

    Article  CAS  PubMed  Google Scholar 

  125. Saruta, T. et al. Efficacy and safety of the selective aldosterone blocker eplerenone in Japanese patients with hypertension: a randomized, double-blind, placebo-controlled, dose-ranging study. J. Clin. Hypertens. (Greenwich) 6, 175–185 (2004).

    Article  CAS  Google Scholar 

  126. Weinberger, M. H., Roniker, B., Krause, S. L. & Weiss, R. J. Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. Am. J. Hypertens. 15, 709–716 (2002).

    Article  CAS  PubMed  Google Scholar 

  127. White, W. B. et al. Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension 41, 1021–1026 (2003).

    Article  CAS  PubMed  Google Scholar 

  128. Pitt, B. et al. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation 108, 1831–1838 (2003).

    Article  CAS  PubMed  Google Scholar 

  129. Weinberger, M. H. et al. Effects of eplerenone versus losartan in patients with low-renin hypertension. Am. Heart J. 150, 426–433 (2005).

    Article  CAS  PubMed  Google Scholar 

  130. Flack, J. M. et al. Efficacy and tolerability of eplerenone and losartan in hypertensive black and white patients. J. Am. Coll. Cardiol. 41, 1148–1155 (2003).

    Article  CAS  PubMed  Google Scholar 

  131. Krum, H. et al. Efficacy of eplerenone added to renin-angiotensin blockade in hypertensive patients. Hypertension 40, 117–123 (2002).

    Article  CAS  PubMed  Google Scholar 

  132. Imanishi, T. et al. Addition of eplerenone to an angiotensin-converting enzyme inhibitor effectively improves nitric oxide bioavailability. Hypertension 51, 734–741 (2008).

    Article  CAS  PubMed  Google Scholar 

  133. Lim, P. O., Jung, R. T. & MacDonald, T. M. Raised aldosterone to renin ratio predicts antihypertensive efficacy of spironolactone: a prospective cohort follow-up study. Br. J. Clin. Pharmacol. 48, 756–760 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Prisant, L. M. et al. Can renin status predict the antihypertensive efficacy of eplerenone add-on therapy? J. Clin. Pharmacol. 43, 1203–1210 (2003).

    Article  CAS  PubMed  Google Scholar 

  135. Mahmud, A., Mahgoub, M., Hall, M. & Feely, J. Does aldosterone-to-renin ratio predict the antihypertensive effect of the aldosterone antagonist spironolactone? Am. J. Hypertens. 18, 1631–1635 (2005).

    Article  CAS  PubMed  Google Scholar 

  136. Weinberger, M. H. The use of selective aldosterone antagonists. Curr. Hypertens. Rep. 6, 342–345 (2004).

    Article  PubMed  Google Scholar 

  137. Burgess, E. Eplerenone in hypertension. Expert Opin. Pharmacother. 5, 2573–2581 (2004).

    Article  CAS  PubMed  Google Scholar 

  138. Jansen, P. M., Danser, A. H., Imholz, B. P. & van den Meiracker, A. H. Aldosterone-receptor antagonism in hypertension. J. Hypertens. 27, 680–691 (2009).

    Article  CAS  PubMed  Google Scholar 

  139. Juurlink, D. N. et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N. Engl. J. Med. 351, 543–551 (2004).

    Article  CAS  PubMed  Google Scholar 

  140. Saha, C. et al. Improvement in blood pressure with inhibition of the epithelial sodium channel in blacks with hypertension. Hypertension 46, 481–487 (2005).

    Article  CAS  PubMed  Google Scholar 

  141. Pratt, J. H., Eckert, G. J., Newman, S. & Ambrosius, W. T. Blood pressure responses to small doses of amiloride and spironolactone in normotensive subjects. Hypertension 38, 1124–1129 (2001).

    Article  CAS  PubMed  Google Scholar 

  142. Ullian, M. E. & Fine, J. J. Mechanisms of enhanced angiotensin II-stimulated signal transduction in vascular smooth muscle by aldosterone. J. Cell. Physiol. 161, 201–208 (1994).

    Article  CAS  PubMed  Google Scholar 

  143. Oberleithner, H. et al. Human endothelium: target for aldosterone. Hypertension 43, 952–956 (2004).

    Article  CAS  PubMed  Google Scholar 

  144. Kidambi, S. et al. Association of adrenal steroids with hypertension and the metabolic syndrome in blacks. Hypertension 49, 704–711 (2007).

    Article  CAS  PubMed  Google Scholar 

  145. Schunkert, H., Hense, H. W., Andus, T., Riegger, G. A. & Straub, R. H. Relation between dehydroepiandrosterone sulfate and blood pressure levels in a population-based sample. Am. J. Hypertens. 12, 1140–1143 (1999).

    Article  CAS  PubMed  Google Scholar 

  146. El-Gharbawy, A. H. et al. Arterial pressure, left ventricular mass, and aldosterone in essential hypertension. Hypertension 37, 845–850 (2001).

    Article  CAS  PubMed  Google Scholar 

  147. Ljungman, S., Aurell, M., Hartford, M., Wikstrand, J. & Berglund, G. Blood pressure in relation to the renin-angiotensin-aldosterone system. Acta Med. Scand. 211, 351–360 (1982).

    Article  CAS  PubMed  Google Scholar 

  148. Lamarre-Cliche, M. et al. Effects of circadian rhythms, posture, and medication on renin-aldosterone interrelations in essential hypertensives. Am. J. Hypertens. 18, 56–64 (2005).

    Article  CAS  PubMed  Google Scholar 

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A. Tomaschitz and S. Pilz have contributed equally in drafting the initial version of this article.

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Tomaschitz, A., Pilz, S., Ritz, E. et al. Aldosterone and arterial hypertension. Nat Rev Endocrinol 6, 83–93 (2010). https://doi.org/10.1038/nrendo.2009.263

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