A lifetime of aldosterone excess: Long-term consequences of altered regulation of aldosterone production for cardiovascular function

Endocrine Reviews

Volumn 29, Issue 2, 2008, Pages 133-154

  Connell, John M C ^a,b   MacKenzie, Scott M ^a   Freel, E Marie ^a   Fraser, Robert ^a   Davies, Eleanor ^a  

^a UNIVERSITY OF GLASGOW   (United Kingdom)

^b UNIVERSITY OF GLASGOW   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALDOSTERONE; ALDOSTERONE SYNTHASE; ALISKIREN; AMLODIPINE; ANGIOTENSIN 2 RECEPTOR ANTAGONIST; CANDESARTAN; CAPTOPRIL; CORTODOXONE; DEOXYCORTICOSTERONE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENALAPRIL; EPLERENONE; FADROZOLE; HYDROCORTISONE; LOSARTAN; MINERALOCORTICOID RECEPTOR; SPIRONOLACTONE; STEROID 11BETA MONOOXYGENASE;

ADRENAL TUMOR; ALDOSTERONE BLOOD LEVEL; ALDOSTERONE RELEASE; ANTIHYPERTENSIVE ACTIVITY; CARDIOVASCULAR FUNCTION; CARDIOVASCULAR RISK; CLINICAL TRIAL; CYP11B1 GENE; CYP11B2 GENE; DRUG MECHANISM; ENVIRONMENTAL FACTOR; ESSENTIAL HYPERTENSION; GENE; GENETIC REGULATION; GENETIC TRANSCRIPTION; GYNECOMASTIA; HEREDITY; HUMAN; HYPERALDOSTERONISM; HYPERTENSION; ISCHEMIC HEART DISEASE; LIBIDO DISORDER; PRIORITY JOURNAL; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW;

ALDOSTERONE; ANIMALS; CARDIOVASCULAR PHYSIOLOGY; HUMANS; HYPERALDOSTERONISM; HYPERTENSION, RENAL; RENIN-ANGIOTENSIN SYSTEM;

EID: 42049107310     PISSN: 0163769X     EISSN: 0163769X     Source Type: Journal    
DOI: 10.1210/er.2007-0030     Document Type: Review

References (238)

1. Simpson SA, Tait JF, Wettstein A, Neher R, von Euw J, Schindler O, Reichstein T 1954 Constitution of aldosterone, a new mineralocorticoid. Experientia 10:132-133
2. Tait SA, Tait JF, Coghlan JP 2004 The discovery, isolation and identification of aldosterone: reflections on emerging regulation and function. Mol Cell Endocrinol 217:1-21
3. Conn JW, Louis LH 1956 Primary aldosteronism, a new clinical entity. Ann Intern Med 44:1-15
4. Stewart PM, Corrie JE, Shackleton CH, Edwards CR 1988 Syndrome of apparent mineralocorticoid excess. A defect in the cortisol-cortisone shuttle. J Clin Invest 82:340-349
5. Funder JW, Pearce PT, Smith R, Smith IA 1988 Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science 242:583-585
6. Driver PM, Rauz S, Walker EA, Hewison M, Kilby MD, Stewart PM 2003 Characterization of human trophoblast as a mineralocorticoid target tissue. Mol Hum Reprod 9:793-798
7. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J 1999 The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 341:709-716
8. Young WF 2007 Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol (Oxf) 66:607-618
9. Orth D, Kovacs W, de Bold C 1992 The adrenal cortex. Williams textbook of endocrinology. Philadelphia: WB Saunders; 489-619
10. Payne AH, Hales DB 2004 Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr Rev 25:947-970
11. Stocco DM 2001 StAR protein and the regulation of steroid hormone biosynthesis. Annu Rev Physiol 63:193-213
12. Lin D, Sugawara T, Strauss 3rd JF, Clark BJ, Stocco DM, Saenger P, Rogol A, Miller WL 1995 Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis. Science 267:1828-1831
13. Lambeth JD, Seybert DW, Lancaster Jr JR, Salerno JC, Kamin H 1982 Steroidogenic electron transport in adrenal cortex mitochondria. Mol Cell Biochem 45:13-31
14. Lieberman S, Lin YY 2001 Reflections on sterol sidechain cleavage process catalyzed by cytochrome P450(scc). J Steroid Biochem Mol Biol 78:1-14
15. Mason JI 1993 The 3β-hydroxysteroid dehydrogenase gene family of enzymes. Trends Endocrinol Metab 4:199-203
16. Simard J, Couet J, Durocher F, Labrie Y, Sanchez R, Breton N, Turgeon C, Labrie F 1993 Structure and tissue-specific expression of a novel member of the rat 3β-hydroxysteroid dehydrogenase/ 5-δ 4 isomerase (3β-HSD) family. The exclusive 3β-HSD gene expression in the skin. J Biol Chem 268:19659-19668
17. Berube D, Luu-The V, Lachance Y, Gagne R, Labrie F 1989 Assignment of the human 3β-hydroxysteroid dehydrogenase gene to the p13 band of chromosome 1. Cytogen Cell Genetics 52:199-200
18. Lachance Y, Luu-The V, Verrault H, Dumont M, Berube E, Lablanc G, Labrie F 1991 Structure of the human type II 3β-hydroxysteroid dehydrogenase/5,4 isomerase (3βHSD) gene: adrenal and gonadal specificity. DNA Cell Biology 10:701-711
19. Shinzawa K, Ishibashi S, Murakoshi M, Watanabe K, Kominami S, Kawahara A, Takemori S 1988 Relationship between zonal distribution of microsomal cytochrome P-450s (P-450(17)α,lyase and P-450C21) and steroidogenic activities in guinea-pig adrenal cortex. J Endocrinol 119:191-200
20. White PC, New MI, Dupont B 1986 Structure of human steroid 21-hydroxylase genes. Proc Natl Acad Sci USA 83:5111-5115
21. Denner K, Doehmer J, Bernhardt R 1995 Cloning of CYP11B1 and CYP11B2 from normal human adrenal and their functional expression in COS-7 and V79 Chinese hamster cells. Endocr Res 21:443-448
22. Mornet E, Dupont J, Vitek A, White PC 1989 Characterization of two genes encoding human steroid 11β-hydroxylase (P-450(11) β). J Biol Chem 264:20961-20967
23. Chua SC, Szabo P, Vitek A, Grzeschik KH, John M, White PC 1987 Cloning of cDNA encoding steroid 11 β-hydroxylase (P450c11). Proc Natl Acad Sci USA 84:7193-7197
24. Wagner M, Ge Y, Siciliano Wells D 1991 A hybrid cell mapping panel for regional localisation of probes to human chromosome 8. Genomics 10:114-125
25. Zhou MY, Gomez-Sanchez EP, Foecking MF, Gomez-Sanchez CE 1995 Cloning and expression of the rat adrenal cytochrome P-450 11B3 (CYP11B3) enzyme cDNA: preferential 18-hydroxylation over 11 β-hydroxylation of DOC. Mol Cell Endocrinol 114:137-145
26. Mellon SH, Bair SR, Monis H 1995 P450c11B3 mRNA, transcribed from a third P450c11 gene, is expressed in a tissue-specific, developmentally, and hormonally regulated fashion in the rodent adrenal and encodes a protein with both 11-hydroxylase and 18-hydroxylase activities. J Biol Chem 270:1643-1649
27. Quinn SJ, Williams GH 1988 Regulation of aldosterone secretion. Annu Rev Physiol 50:409-426
28. Muller J 1987 Regulation of aldosterone biosynthesis. Physiological and clinical aspects. Monogr Endocrinol 29:1-364
29. Lavoie JL, Sigmund CD 2003 Minireview: overview of the reninangiotensin system-an endocrine and paracrine system. Endocrinology 144:2179-2183
30. Samani NJ 1994 Extrarenal renin-angiotensin systems. In: Swales JD, ed. Textbook of hypertension. Oxford, UK: Blackwell Scientific Publications; 253-272
31. MacKenzie SM, Fraser R, Connell JMC, Davies E 2002 Local renin-angiotensin systems and their interactions with extra-adrenal corticosteroid production. J Renin Angiotensin Aldosterone Syst 3:214-221
32. Sugiyama T, Yoshimoto T, Tsuchiya K, Gochou N, Hirono Y, Tateno T, Fukai N, Shichiri M, Hirata Y 2005 Aldosterone induces angiotensin converting enzyme gene expression via a JAK2-dependent pathway in rat endothelial cells. Endocrinology 146:3900-3906
33. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S 2000 A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res 87:E1-E9
34. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ 2000 A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 275:33238-33243
35. Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, de Buhr I, Heringer-Walther S, Pinheiro SV, Lopes MT, Bader M, Mendes EP, Lemos VS, Campagnole-Santos MJ, Schultheiss HP, Speth R, Walther T 2003 Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci USA 100:8258-8263
36. Chappell MC 2007 Emerging evidence for a functional angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS receptor axis: more than regulation of blood pressure? Hypertension 50:596-599
37. Raizada MK, Ferreira AJ 2007 ACE2: a new target for cardiovascular disease therapeutics. J Cardiovasc Pharmacol 50:112-119
38. Spät A, Hunyady L 2004 Control of aldosterone secretion: a model for convergence in cellular signaling pathways. Physiol Rev 84: 489-539
39. Bassett MH, White PC, Rainey WE 2004 The regulation of aldosterone synthase expression. Mol Cell Endocrinol 217:67-74
40. Bassett MH, White PC, Rainey WE 2004 A role for the NGFI-B family in adrenal zonation and adrenocortical disease. Endocr Res 30:567-574
41. Spät A 2004 Glomerulosa cell-a unique sensor of extracellular K+ concentration. Mol Cell Endocrinol 217:23-26
42. Clyne CD, Zhang Y, Slutsker L, Mathis JM, White PC, Rainey WE 1997 Angiotensin II and potassium regulate human CYP11B2 transcription through common cis-elements. Mol Endocrinol 11:638-649
43. Veldhuis JD, Iranmanesh A, Johnson ML, Lizarralde G 1990 Twenty-four-hour rhythms in plasma concentrations of adenohypophyseal hormones are generated by distinct amplitude and/or frequency modulation of underlying pituitary secretory bursts. J Clin Endocrinol Metab 71:1616-1623
44. Sala GB, Hayashi K, Catt KJ, Dufau ML 1979 Adrenocorticotropin action in isolated adrenal cells. The intermediate role of cyclic AMP in stimulation of corticosterone synthesis. J Biol Chem 254:3861-3865
45. Mountjoy KG, Robbins LS, Mortrud MT, Cone RD 1992 The cloning of a family of genes that encode the melanocortin receptors. Science 257:1248-1251
46. Arola J, Heikkila P, Voutilainen R, Kahri AI 1994 Protein kinase C signal transduction pathway in ACTH-induced growth effect of rat adrenocortical cells in primary culture. J Endocrinol 141:285-293
47. Yamazaki T, Higuchi K, Kominami S, Takemori S 1996 15-lipoxygenase metabolite(s) of arachidonic acid mediates adrenocorticotropin action in bovine adrenal steroidogenesis. Endocrinology 137:2670-2675
48. Yamazaki T, Kimoto T, Higuchi K, Ohta Y, Kawato S, Kominami S 1998 Calcium ion as a second messenger for o-nitrophenylsulfenyl-adrenocorticotropin (NPS-ACTH) and ACTH in bovine adrenal steroidogenesis. Endocrinology 139:4765-4771
49. Waterman MR, Bischof LJ 1996 Mechanisms of ACTH(cAMP)-dependent transcription of adrenal steroid hydroxylases. Endocr Res 22:615-620
50. Bornstein SR, Ehrhart-Bornstein M, Scherbaum WA 1996 The adrenal gland and ACTH. Eur J Endocrinol 135:739
51. Vinson GP 2003 Adrenocortical zonation and ACTH. Microsc Res Tech 61:227-239
52. Arola J, Heikkila P, Voutilainen R, Kahri AI 1993 Role of adenylate cyclase-cyclic AMP-dependent signal transduction in the ACTH-induced biphasic growth effect of rat adrenocortical cells in primary culture. J Endocrinol 139:451-461
53. Fuchs-Hammoser R, Schweiger M, Oelkers W 1980 The effect of chronic low-dose infusion of ACTH (1-24) on renin, renin- substrate, aldosterone and other corticosteroids in sodium replete and deplete man. Acta Endocrinol (Copenh) 95:198-206
54. Holland OB, Carr B 1993 Modulation of aldosterone synthase messenger ribonucleic acid levels by dietary sodium and potassium and by adrenocorticotropin. Endocrinology 132:2666-2673
55. Aguilera G, Kiss A, Lu A, Camacho C 1996 Regulation of adrenal steroidogenesis during chronic stress. Endocr Res 22:433-443
56. Yoshida A, Nishikawa T, Tamura Y, Yoshida S 1991 ACTH-induced inhibition of the action of angiotensin II in bovine zona glomerulosa cells. A modulatory effect of cyclic AMP on the angiotensin II receptor. J Biol Chem 266:4288-4294
57. Bird IM, Mason JI, Rainey WE 1994 Regulation of type 1 angiotensin II receptor messenger ribonucleic acid expression in human adrenocortical carcinoma H295 cells. Endocrinology 134:2468-2474
58. McAllister JM, Hornsby PJ 1988 Dual regulation of 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase, and dehydroepiandrosterone sulfotransferase by adenosine 3′,5′- monophosphate and activators of protein kinase C in cultured human adrenocortical cells. Endocrinology 122:2012-2018
59. Bird IM, Pasquarette MM, Rainey WE, Mason JI 1996 Differential control of 17α-hydroxylase and 3β-hydroxysteroid dehydrogenase expression in human adrenocortical H295R cells. J Clin Endocrinol Metab 81:2171-2178
60. Richards AM, Nicholls MG, Espiner EA, Ikram H, Cullens M, Hinton D 1986 Diurnal patterns of blood pressure, heart rate and vasoactive hormones in normal man. Clin Exp Hypertens A 8:153-166
61. Coll AP, Challis BG, Yeo GS, Snell K, Piper SJ, Halsall D, Thresher RR, O'Rahilly S 2004 The effects of proopiomelanocortin deficiency on murine adrenal development and responsiveness to adrenocorticotropin. Endocrinology 145:4721-4727
62. Lin L, Hindmarsh PC, Metherell LA, Alzyoud M, Al Ali M, Brain CE, Clark AJ, Dattani MT, Achermann JC 2007 Severe loss-offunction mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia. Clin Endocrinol (Oxf) 66:205-210
63. Davies E, MacKenzie SM 2003 Extra-adrenal production of corticosteroids. Clin Exp Pharmacol Physiol 30:437-445
64. Mellon SH, Deschepper CF 1993 Neurosteroid biosynthesis: genes for adrenal steroidogenic enzymes are expressed in the brain. Brain Res 629:283-292
65. Stromstedt M, Waterman MR 1995 Messenger RNAs encoding steroidogenic enzymes are expressed in rodent brain. Brain Res Mol Brain Res 34:75-88
66. Gomez-Sanchez CE, Zhou MY, Cozza EN, Morita H, Eddleman FC, Gomez-Sanchez EP 1996 Corticosteroid synthesis in the central nervous system. Endocr Res 22:463-470
67. MacKenzie SM, Clark CJ, Ingram MC, Lai M, Seckl J, Gomez-Sanchez CE, Fraser R, Connell JM, Davies E 2000 Corticosteroid production by fetal rat hippocampal neurons. Endocr Res 26:531-535
68. Furukawa A, Miyatake A, Ohnishi T, Ichikawa Y 1998 Steroidogenic acute regulatory protein (StAR) transcripts constitutively expressed in the adult rat central nervous system: colocalization of StAR, cytochrome P-450SCC (CYP XIA1), and 3β- hydroxysteroid dehydrogenase in the rat brain. J Neurochem 71:2231-2238
69. Ye P, Kenyon CJ, MacKenzie SM, Seckl JR, Fraser R, Connell JMC, Davies E 2003 Regulation of aldosterone synthase gene expression in the rat adrenal gland and central nervous system by sodium and angiotensin II. Endocrinology 144:3321-3328
70. Yu L, Romero DG, Gómez-Sánchez CE, Gómez- Sánchez EP 2002 Steroidogenic enzyme gene expression in the human brain. Mol Cell Endocrinol 190:9-17
71. Sharma KK, Lindqvist A, Zhou XJ, Auchus RJ, Penning TM, Andersson S 2006 Deoxycorticosterone inactivation by AKR1C3 in human mineralocorticoid target tissues. Mol Cell Endocrinol 248:79-86
72. Takeda Y, Miyamori I, Yoneda T, Iki K, Hatakeyama H, Blair IA, Hsieh F-Y, Takeda R 1995 Production of aldosterone in isolated rat blood vessels. Hypertension 25:170-173
73. Takeda Y, Miyamori I, Yoneda T, Hatakeyama H, Inaba S, Furukawa K, Mabuchi H, Takeda R 1996 Regulation of aldosterone synthase in human vascular endothelial cells by angiotensin II and adrenocorticotropin. J Clin Endocrinol Metab 81:2797-2800
74. Ahmad N, Romero DG, Gomez-Sanchez EP, Gomez-Sanchez CE 2004 Do human vascular endothelial cells produce aldosterone? Endocrinology 145:3626-3629
75. Silvestre J-S, Robert V, Heymes C, Aupetit-Faisant B, Mouas C, Moalic J-M, Swynghedauw B, Delcayre C 1998 Myocardial production of aldosterone and corticosterone in the rat. J Biol Chem 237:4883-4891
76. Takeda Y, Yoneda T, Demura M, Miyamori I, Mabuchi H 2000 Cardiac aldosterone production in genetically hypertensive rats. Hypertension 36:495-500
77. Rudolph AE, Blasi ER, Delyani JA 2000 Tissue-specific corticosteroidogenesis in the rat. Mol Cell Endocrinol 165:221-224
78. Ye P, Kenyon C, MacKenzie SM, Jong AS, Miller C, Gray GA, Wallace AM, Ryding ADS, Mullins JJ, McBride MW, Graham D, Fraser R, Connell JMC, Davies E 2005 The aldosterone synthase (CYP11B2) and 11β-hydroxylase (CYP11B1) genes are not expressed in the rat heart. Endocrinology 146:5287-5293
79. Gomez-Sanchez EP, Ahmad N, Romero DG, Gomez-Sanchez CE 2004 Origin of aldosterone in the rat heart. Endocrinology 145:4796-4802
80. Kayes-Wandover KM, White PC 2000 Steroidogenic enzyme gene expression in the human heart. J Clin Endocrinol Metab 85:2519-2525
81. Pezzi V, Mathis JM, Rainey WE, Carr BR 2003 Profiling transcript levels for steroidogenic enzymes in fetal tissues. J Steroid Biochem Mol Biol 87:181-189
82. Young MJ, Clyne CD, Cole TJ, Funder JW 2001 Cardiac steroidogenesis in the normal and failing heart. J Clin Endocrinol Metab 86:5121-5126
83. Mizuno Y, Yoshimura M, Yasue H, Sakamoto T, Ogawa H, Kugiyama K, Harada E, Nakayama M, Nakamura S, Ito T, Shimasaki Y, Saito Y, Nakao K 2001 Aldosterone production is activated in failing ventricle in humans. Circulation 103:72-77
84. Yamamoto N, Yasue H, Mizuno Y, Yoshimura M, Fujii H, Nakayama M, Harada E, Nakamura S, Ito T, Ogawa H 2002 Aldosterone is produced from ventricles in patients with essential hypertension. Hypertension 39:958-962
85. Tsutamoto T, Wada A, Maeda K, Mabuchi N, Hayashi M, Tsutsui T, Ohnishi M, Sawaki M, Fujii M, Matsumoto T, Horie H, Sugimoto Y, Kinoshita M 2002 Transcardiac extraction of circulating endothelin-1 across the failing heart. Am J Cardiol 86:524-528
86. White PC 2003 Aldosterone: direct effects on and production by the heart. J Clin Endocrinol Metab 88:2376-2383
87. Yao L, Lici YL, Wilhelm-Bhagat CG, Romero DG, Gomez-Sanchez CE, Gomez-Sanchez EP Over-expression of aldosterone synthase in neurons is associated with hypertension but not systemic aldosterone elevation. Program of the Endocrine Society's 89th Annual Meeting, Toronto, Canada, 2007 (Abstract OR31-5)
88. Hu X, Funder JW 2006 The evolution of mineralocorticoid receptors. Mol Endocrinol 20:1471-1478
89. Arriza JL, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman DE, Evans RM 1987 Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science 237:268-275
90. Rogerson FM, Brennan FE, Fuller PJ 2004 Mineralocorticoid receptor binding, structure and function. Mol Cell Endocrinol 217:203-212
91. Geering K, Beguin P, Garty H, Karlish SJ, Fuzesi M, Horisberger JD, Crambert G 2003 FXYD proteins: new tissue-and isoformspecific regulators of Na, K-ATPase. Ann NY Acad Sci 986:388-394
92. Stockand JD 2002 New ideas about aldosterone signaling in epithelia. Am J Physiol Renal Physiol 282:F559-F576
93. Blazer-Yost BL, Liu X, Helman SI 1998 Hormonal regulation of ENaCs: insulin and aldosterone. Am J Physiol 274:1373-1379
94. Blazer-Yost BL, Paunescu TG, Helman SI, Lee KD, Vlahos CJ 1999 Phosphoinositide 3-kinase is required for aldosterone-regulated sodium reabsorption. Am J Physiol 277:531-536
95. Stockand JD, Meszaros JG 2003 Aldosterone stimulates proliferation of cardiac fibroblasts by activating Ki-RasA and MAPK1/2 signaling. Am J Physiol Heart Circ Physiol 284:176-184
96. Pearce D, Kleyman TR 2007 Salt, sodium channels, and SGK1. J Clin Invest 117:592-595
97. Diakov A, Korbmacher C 2004 A novel pathway of epithelial sodium channel activation involves a serum- and glucocorticoid-inducible kinase consensus motif in the C terminus of the channel's α-subunit. J Biol Chem 279:38134-38142
98. Pearce D 2003 SGK1 regulation of epithelial sodium transport. Cell Physiol Biochem 13:13-20
99. Synder PM, Olson DR, Thomas BC 2002 Serum and glucocorticoid- regulated kinase modulate Nedd4-2 mediated inhibition of the epithelial Na+ channel. J Biol Chem 277:5-8
100. Zhang W, Xia X, Reisenauer MR, Rieg T, Lang F, Kuhl D, Vallon V, Kone BC 2007 Aldosterone-induced Sgk1 relieves Dot1a-Af9-mediated transcriptional repression of epithelial Na+ channel α. J Clin Invest 117:773-783
101. Bhalla V, Soundararajan R, Pao AC, Li H, Pearce D 2006 Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ. Am J Physiol Renal Physiol 291:F714-F721
102. Funder J, Myles K 1996 Exclusion of corticosterone from epithelial mineralocorticoid receptors is insufficient for selectivity of aldosterone action: in vivo binding studies. Endocrinology 137:5264-5268
103. Young M, Funder JW 2000 Aldosterone and the heart. Trends Endocrinol Metab 11:224-226
104. Qin W, Rudolph AE, Bond BR, Rocha R, Blomme EA, Goellner JJ, Funder JW, McMahon EG 2003 Transgenic model of aldosterone-driven cardiac hypertrophy and heart failure. Circ Res 93:69-76
105. Gomez-Sanchez EP 1986 Intracerebroventricular infusion of aldosterone induces hypertension in rats. Endocrinology 118:819-823
106. Gomez-Sanchez EP, Fort CM, Gomez-Sanchez CE 1990 Intracerebroventricular infusion of RU28318 blocks aldosterone-salt hypertension. Am J Physiol 258:482-484
107. Robson AC, Leckie CM, Seckl JR, Holmes MC 1998 11β-Hydroxysteroid dehydrogenase type 2 in the postnatal and adult rat brain. Mol Brain Res 61:1-10
108. Seckl JR 1997 11β-Hydroxysteroid dehydrogenase in the brain: a novel regulator of glucocorticoid action? Front Neuroendocrinol 18:49-99
109. Geerling JC, Kawata M, Loewy AD 2006 Aldosterone-sensitive neurons in the rat central nervous system. J Comp Neurol 494:515-527
110. Broadwell RD, Sofroniew MV 1993 Serum proteins bypass the blood-brain fluid barriers for extracellular entry to the central nervous system. Exp Neurol 120:245-263
111. Takebayashi K, Matsumoto S, Aso Y, Inukai T 2006 Aldosterone blockade attenuates urinary monocyte chemoattractant protein-1 and oxidative stress in patients with type 2 diabetes complicated by diabetic nephropathy. J Clin Endocrinol Metab 91:2214-2217
112. Kraus D, Jager J, Meier B, Fasshauer M, Klein J 2005 Aldosterone inhibits uncoupling protein-1, induces insulin resistance, and stimulates proinflammatory adipokines in adipocytes. Horm Metab Res 37:455-459
113. Rocha R, Rudolph AE, Frierdich GE, Nachowiak DA, Kekec BK, Blomme EA, McMahon EG, Delyani JA 2002 Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol 283:H1802-H1810
114. Fiebeler A, Schmidt F, Muller DN, Park JK, Dechend R, Bieringer M, Shagdarsuren E, Breu V, Haller H, Luft FC 2001 Mineralocorticoid receptor affects AP-1 and nuclear factor-κB activation in angiotensin II-induced cardiac injury. Hypertension 37:787-793
115. Sanz-Rosa D, Cediel E, de las Heras N, Miana M, Balfagon G, Lahera V, Cachofeiro V 2005 Participation of aldosterone in the vascular inflammatory response of spontaneously hypertensive rats: role of the NFκB/IκB system. J Hypertens 23:1167-1172
116. Johar S, Cave AC, Narayanapanicker A, Grieve DJ, Shah AM 2006 Aldosterone mediates angiotensin II-induced interstitial cardiac fibrosis via a Nox2-containing NADPH oxidase. FASEB J 20:1546-1548
117. White PC 2004 Aldosterone synthase deficiency and related disorders. Mol Cell Endocrinol 217:81-87
118. Berger S, Bleich M, Schmid W, Cole TJ, Peters J, Watanabe H, Kriz W, Warth R, Greger R, Schutz G 1998 Mineralocorticoid receptor knockout mice: pathophysiology of Na+ metabolism. Proc Natl Acad Sci USA 95:9424-9429
119. Makhanova N, Sequeira-Lopez ML, Gomez RA, Kim HS, Smithies O 2006 Disturbed homeostasis in sodium-restricted mice heterozygous and homozygous for aldosterone synthase gene disruption. Hypertension 48:1151-1159
120. Vasan RS, Evans JC, Larson MG, Wilson PW, Meigs JB, Rifai N, Benjamin EJ, Levy D 2004 Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N Engl J Med 351:33-41
121. Reynolds R, Walker B, Phillips D, Sydall H, Davies E, Fraser R, Connell JM 2007 Acute aldosterone responses to ACTH predict both cortisol responses and blood pressure. Endocr Abstracts 13:OC24
122. Mulatero P, Stowasser M, Loh KC, Fardella CE, Gordon RD, Mosso L, Gomez-Sanchez CE, Veglio F, Young Jr WF 2004 Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab 89:1045-1050
123. Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C, Ganzaroli C, Giacchetti G, Letizia C, Maccario M, Mallamaci F, Mannelli M, Mattarello MJ, Moretti A, Palumbo G, Parenti G, Porteri E, Semplicini A, Rizzoni D, Rossi E, Boscaro M, Pessina AC, Mantero F 2006 A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol 48:2293-2300
124. Montori VM, Young Jr WF 2002 Use of plasma aldosterone concentration-to-plasma renin activity ratio as a screening test for primary aldosteronism. A systematic review of the literature. Endocrinol Metab Clin North Am 31:619-632
125. Calhoun DA, Nishizaka MK, Zaman MA, Thakkar RB, Weissmann P 2002 Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 40:892-896
126. Young Jr WF 2003 Minireview: primary aldosteronism-changing concepts in diagnosis and treatment. Endocrinology 144:2208-2213
127. Padfield PL, Brown JJ, Davies D, Fraser R, Lever AF, Morton JJ, Robertson JI 1981 The myth of idiopathic hyperaldosteronism. Lancet 2:83-84
128. Brunner HR, Sealey JE, Laragh JH 1973 Renin subgroups in essential hypertension. Further analysis of their pathophysiological and epidemiological characteristics. Circ Res 32(Suppl 1):99-105
129. Padfield PL, Brown JJ, Lever AF, Schalekamp MA, Beevers DG, Davies DL, Robertson JI, Tree M 1975 Is low-renin hypertension a stage in the development of essential hypertension or a diagnostic entity? Lancet 1:548-550
130. Beevers DG, Brown JJ, Cuesta V, Davies DL, Fraser R, Lebel M, Lever AF, Morton JJ, Oelkers W, Robertson JI, Schalekamp MA, Tree M 1975 Inter-relationships between plasma angiotensin II, arterial pressure, aldosterone and exchangeable sodium in normotensive and hypertensive man. J Steroid Biochem 6:779-784
131. Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ 2005 Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 45:1243-1248
132. Duprez DA, Bauwens FR, De Buyzere ML, De Backer TL, Kaufman JM, Van Hoecke J, Vermeulen A, Clement DL 1993 Influence of arterial blood pressure and aldosterone on left ventricular hypertrophy in moderate essential hypertension. Am J Cardiol 71:17A-20A
133. Beygui F, Collet JP, Benoliel JJ, Vignolles N, Dumaine R, Barthelemy O, Montalescot G 2006 High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST-elevation myocardial infarction. Circulation 114:2604-2610
134. Dzau VJ, Bernstein K, Celermajer D, Cohen J, Dahlof B, Deanfield J, Diez J, Drexler H, Ferrari R, van Gilst W, Hansson L, Hornig B, Husain A, Johnston C, Lazar H, Lonn E, Luscher T, Mancini J, Mimran A, Pepine C, Rabelink T, Remme W, Ruilope L, Ruzicka M, Schunkert H, Swedberg K, Unger T, Vaughan D, Weber M 2001 The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data. Am J Cardiol 88:1L-20L
135. Swedberg K, Eneroth P, Kjekshus J, Snapinn S 1990 Effects of enalapril and neuroendocrine activation on prognosis in severe congestive heart failure (follow-up of the CONSENSUS trial). CONSENSUS Trial Study Group. Am J Cardiol 66:40D-44D
136. Vantrimpont P, Rouleau JL, Ciampi A, Harel F, de Champlain J, Bichet D, Moye LA, Pfeffer M 1998 Two-year time course and significance of neurohumoral activation in the Survival and Ventricular Enlargement (SAVE) Study. Eur Heart J 19:1552-1563
137. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Rittman R, Hurley S, Kleiman J, Gatlin M, Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators 2003 Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348:1309-1321
138. McKelvie RS, Yusuf S, Pericak D, Avezum A, Burns RJ, Probstfield J, Tsuyuki RT, White M, Rouleau J, Latini R, Maggioni A, Young J, Pogue J 1999 Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 100:1056-1064
139. Brilla CG, Pick R, Tan LB, Janicki JS, Weber KT 1990 Remodeling of the rat right and left ventricles in experimental hypertension. Circ Res 67:1355-1364
140. Weber KT, Brilla CG 1991 Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation 83:1849-1865
141. Brilla CG, Matsubara LS, Weber KT 1993 Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. J Mol Cell Cardiol 25:563-575
142. Young M, Funder JW 2004 Eplerenone, but not steroid withdrawal, reverses cardiac fibrosis in deoxycorticosterone/salt-treated rats. Endocrinology 145:3153-3157
143. Brilla CG, Weber KT 1992 Mineralocorticoid excess, dietary sodium, and myocardial fibrosis. J Lab Clin Med 120:893-901
144. Funder JW 2004 Aldosterone, mineralocorticoid receptors and vascular inflammation. Mol Cell Endocrinol 217:263-269
145. Nagase M, Matsui H, Shibata S, Gotoda T, Fujita T 2007 Salt-induced nephropathy in obese spontaneously hypertensive rats via paradoxical activation of the mineralocorticoid receptor: role of oxidative stress. Hypertension 50:877-883
146. Funder JW 2007 Mineralocorticoid receptor activation and oxidative stress. Hypertension 50:840-841
147. Rocha R, Stier Jr CT 2001 Pathophysiological effects of aldosterone in cardiovascular tissues. Trends Endocrinol Metab 12:308-314 148. Funder JW 1995 Steroids, hypertension and cardiac fibrosis. Blood Press 4:39-42
148. Robert V, van Thiem N, Cheav SL, Mouas C, Swynghedauw B, Delcayre C 1994 Increased cardiac types I and III collagen mRNAs in aldosterone-salt hypertension. Hypertension 24:30-36
149. Young M, Funder J 2003 Mineralocorticoid action and sodium-hydrogen exchange: studies in experimental cardiac fibrosis. Endocrinology 144:3848-3851
150. Zannad F, Alla F, Dousset B, Perez A, Pitt B 2000 Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation 102:2700-2706
151. Sun Y, Zhang J, Lu L, Chen SS, Quinn MT, Weber KT 2002 Aldosterone-induced inflammation in the rat heart: role of oxidative stress. Am J Pathol 161:1773-1781
152. Kang YM, Zhang ZH, Johnson RF, Yu Y, Beltz T, Johnson AK, Weiss RM, Felder RB 2006 Novel effect of mineralocorticoid receptor antagonism to reduce proinflammatory cytokines and hypothalamic activation in rats with ischemia-induced heart failure. Circ Res 99:758-766
153. Rocha R, Chander PN, Zuckerman A, Stier Jr CT 1999 Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. Hypertension 33:232-237
154. Epstein M, Williams GH, Weinberger M, Lewin A, Krause S, Mukherjee R, Patni R, Beckerman B 2006 Selective aldosterone blockade with eplerenone reduces albuminuria in patients with type 2 diabetes. Clin J Am Soc Nephrol 1:940-951
155. Rocha R, Chander PN, Khanna K, Zuckerman A, Stier Jr CT 1998 Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats. Hypertension 31:451-458
156. Litchfield WR, Anderson BF, Weiss RJ, Lifton RP, Dluhy RG 1998 Intracranial aneurysm and hemorrhagic stroke in glucocorticoid-remediable aldosteronism. Hypertension 31:445-450
157. Macdonald JE, Kennedy N, Struthers AD 2004 Effects of spironolactone on endothelial function, vascular angiotensin converting enzyme activity, and other prognostic markers in patients with mild heart failure already taking optimal treatment. Heart 90:765-770
158. Struthers AD 2004 Aldosterone-induced vasculopathy. Mol Cell Endocrinol 217:239-241
159. Fallo F, Della MP, Sonino N, Bertello C, Ermani M, Vettor R, Veglio F, Mulatero P 2007 Adiponectin and insulin sensitivity in primary aldosteronism. Am J Hypertens 20:855-861
160. Colussi G, Catena C, Lapenna R, Nadalini E, Chiuch A, Sechi LA 2007 Insulin resistance and hyperinsulinemia are related to plasma aldosterone levels in hypertensive patients. Diabetes Care 30:2349-2354
161. Luther JM, Gainer JV, Murphey LJ, Yu C, Vaughan DE, Morrow JD, Brown NJ 2006 Angiotensin II induces interleukin-6 in humans through a mineralocorticoid receptor-dependent mechanism. Hypertension 48:1050-1057
162. Newton-Cheh C, Guo CY, Gona P, Larson MG, Benjamin EJ, Wang TJ, Kathiresan S, O'Donnell CJ, Musone SL, Camargo AL, Drake JA, Levy D, Hirschhorn JN, Vasan RS 2007 Clinical and genetic correlates of aldosterone-to-renin ratio and relations to blood pressure in a community sample. Hypertension 49:846-856
163. Oelkers W, Brown JJ, Fraser R, Lever AF, Morton JJ, Robertson JIS 1974 Sensitization of the adrenal cortex to angiotensin II in sodium-deplete man. Circ Res 69-77
164. Hollenberg NK, Williams G, Burger B, Hooshmand I 1975 The influence of potassium on the renal vasculature and the adrenal gland, and their responsiveness to angiotensin II in normal man. Clin Sci Mol Med 49:527-534
165. Kathiresan S, Larson MG, Benjamin EJ, Corey D, Murabito JM, Fox CS, Wilson PW, Rifai N, Meigs JB, Ricken G, Lifton RP, Levy D, Vasan RS 2005 Clinical and genetic correlates of serum aldosterone in the community: the Framingham Heart Study. Am J Hypertens 18:657-665
166. Weidmann P, Myttenaere-Bursztein S, Maxwell MH, de Lima J 1975 Effect of aging on plasma renin and aldosterone in normal man. Kidney Int 8:325-333
167. Weidmann P, Beretta-Piccoli C, Ziegler WH, Keusch G, Gluck Z, Reubi FC 1978 Age versus urinary sodium for judging renin, aldosterone, and catecholamine levels: studies in normal subjects and patients with essential hypertension. Kidney Int 14:619-628
168. Olivieri O, Ciacciarelli A, Signorelli D, Pizzolo F, Guarini P, Pavan C, Corgnati A, Falcone S, Corrocher R, Micchi A, Cressoni C, Blengio G 2004 Aldosterone to renin ratio in a primary care setting: the Bussolengo study. J Clin Endocrinol Metab 89:4221-4226
169. Tsunoda K, Abe K, Goto T, Yasujima M, Sato M, Omata K, Seino M, Yoshinaga K 1986 Effect of age on the renin-angiotensin-aldosterone system in normal subjects: simultaneous measurement of active and inactive renin, renin substrate, and aldosterone in plasma. J Clin Endocrinol Metab 62:384-389
170. James VH, Tunbridge RD, Wilson GA 1976 Studies on the control of aldosterone secretion in man. J Steroid Biochem 7:941-948
171. Luft FC, Rankin LI, Bloch R, Weyman AE, Willis LR, Murray RH, Grim CE, Weinberger MH 1979 Cardiovascular and humoral responses to extremes of sodium intake in normal black and white men. Circulation 60:697-706
172. Weidmann P, De Chatel R, Schiffmann A, Bachmann E, Beretta-Piccoli C, Reubi FC, Ziegler WH, Vetter W 1977 Interrelations between age and plasma renin, aldosterone and cortisol, urinary catecholamines, and the body sodium/volume state in normal man. Klin Wochenschr 55:725-733
173. Goodfriend TL, Egan BM, Kelley DE 1998 Aldosterone in obesity. Endocr Res 24:789-796
174. Inglis GC, Ingram MC, Holloway CD, Swan L, Birnie D, Hillis WS, Davies E, Fraser R, Connell JMC 1999 Familial pattern of corticosteroids and their metabolism in adult human subjects-the Scottish adult twin study. J Clin Endocrinol Metab 84:4132-4137
175. Kotchen TA, Kotchen JM, Grim CE, George V, Kaldunski ML, Cowley AW, Hamet P, Chelius TH 2000 Genetic determinants of hypertension: identification of candidate phenotypes. Hypertension 36:7-13
176. Imrie H, Freel M, Mayosi BM, Davies E, Fraser R, Ingram M, Cordell HJ, Farrall M, Avery PJ, Watkins H, Keavney B, Connell JM 2006 Association between aldosterone production and variation in the 11β-hydroxylase (CYP11B1) gene. J Clin Endocrinol Metab 91:5051-5056
177. Rapp JP, Dahl LK 1972 Possible role of 18-hydroxy- deoxycorticosterone in hypertension. Nature 237:338-339
178. Cicila G, Rapp JR, Wang J-M, St Lezin E, Ng S, Kurtz TW 1993 Linkage of 11β-hydroxylase mutations with altered steroid biosynthesis and blood pressure in Dahl rat. Nat Genet 3:346-353
179. Cover CM, Wang JM, St Lezin E, Kurtz T, Mellon SH 1995 Molecular variants in the P450c11AS gene as determinants of aldosterone synthase activity in the Dahl rat model of hypertension. J Biol Chem 270:16555-16560
180. Sutherland DJ, Ruse JL, Laidlaw JC 1966 Hypertension, increased aldosterone secretion and low plasma renin activity relieved by dexamethasone. Can Med Assoc J 95:1109-1119
181. Rich GM, Ulick S, Cook S, Wang JZ, Lifton RP, Dluhy RG 1992 Glucocorticoid-remediable aldosteronism in a large kindred: clinical spectrum and diagnosis using a characteristic biochemical phenotype. Ann Intern Med 116:813-820
182. Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S, Ulick S, Lalouel J-M 1992 A chimaeric 11β-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature 355:262-265
183. White PC, Curnow KM, Pascoe L 1994 Disorders of steroid 11β-hydroxylase isozymes. Endocr Rev 15:421-438
184. White PC, Slutsker L 1995 Haplotype analysis of CYP11B2. Endocr Res 21:437-442
185. Bassett MH, Zhang Y, Clyne C, White PC, Rainey WE 2002 Differential regulation of aldosterone synthase and 11β-hydroxylase transcription by steroidogenic factor-1. J Mol Endocrinol 28:125-135
186. Davies E, Holloway CD, Ingram MC, Inglis GC, Friel EC, Morrison C, Anderson NH, Fraser R, Connell JMC 1999 Aldosterone excretion rate and blood pressure in essential hypertension are related to polymorphic differences in the aldosterone synthase gene CYP11B2. Hypertension 33:703-707
187. Brand E, Chatelain N, Mulatero P, Fery I, Curnow K, Jeunemaitre X, Corvol P, Pascoe L, Soubrier F 1998 Structural analysis and evaluation of the aldosterone synthase gene in hypertension. Hypertension 32:198-204
188. Paillard F, Chansel D, Brand E, Benetos A, Thomas F, Czekalski S, Ardaillou R, Soubrier F 1999 Genotype-phenotype relationships for the renin-angiotensin-aldosterone system in a normal population. Hypertension 34:423-429
189. Komiya I, Yamada T, Takara M, Asawa T, Shimabukuro M, Nishimori T, Takasu N 2000 Lys173Arg and -344T/C variants of CYP11B2 in Japanese patients with low-renin hypertension. Hypertension 35:699-703
190. Lim PO, MacDonald TM, Holloway CD, Friel EC, Anderson NH, Dow E, Jung RT, Davies E, Fraser R, Connell JMC 2002 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
191. Pojoga L, Gautier S, Blanc H, Guyene TT, Poirier O, Cambien F, Benetos 1998 Genetic determination of plasma aldosterone levels in essential hypertension. Am J Hypertens 11:856-860
192. Tsujita Y, Iwai N, Katsuya T, Higaki J, Ogihara T, Tamaki S, Kinoshita M, Mannami T, Ogata J, Baba S 2001 Lack of association between genetic polymorphism of CYP11B2 and hypertension in Japanese: the Suita study. Hypertens Res 24:105-109
193. Sookoian S, Gianotti TF, Gonzalez CD, Pirola CJ 2007 Association of the C-344T aldosterone synthase gene variant with essential hypertension: a meta-analysis. J Hypertens 25:5-13
194. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI 2007 A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889-894
195. Fardella CE, Hum DW, Rodriguez H, Zhang G, Barry FL, Ilicki A, Bloch, CA, Miller WL 1996 Gene conversion in the CYP11B2 gene encoding P450c11AS is associated with, but does not cause, the syndrome of corticosterone methyloxidase II deficiency. J Clin Endocrinol Metab 81:321-326
196. Fardella CE, Rodriguez H, Montero J, Zhang G, Vignolo P, Rojas A, Villarroel L, Miller WL 1996 Genetic variation in P450c11AS in Chilean patients with low renin hypertension. J Clin Endocrinol Metab 81:4347-4351
197. Tanahashi H, Mune T, Takahashi Y, Isaji M, Suwa T, Morita H, Yamakita N, Yasuda K, Deguchi T, White PC, Takeda J 2005 Association of Lys173Arg polymorphism with CYP11B2 expression in normal adrenal glands and aldosterone-producing adenomas. J Clin Endocrinol Metab 90:6226-6231
198. Keavney B, Mayosi B, Gaukrodger N, Imrie H, Baker M, Fraser R, Ingram M, Watkins H, Farrall M, Davies E, Connell J 2005 Genetic variation at the locus encompassing 11-β hydroxylase and aldosterone synthase accounts for heritability in cortisol precursor (11-deoxycortisol) urinary metabolite excretion. J Clin Endocrinol Metab 90:1072-1077
199. Kaplan NM 2001 Cautions over the current epidemic of primary aldosteronism. Lancet 357:953-954
200. de Simone G, Tommaselli A, Rossi R, Valentino R, Lauria R, Scopacasa F, Lombardi G 1985 Partial deficiency of adrenal 11β-hydroxylase - a possible cause of primary hypertension. Hypertension 7:613-618
201. Hautanena A, Lankinen L, Kupari M, Janne OA, Adlercreutz H, Nikkila H, White PC 1998 Associations between aldosterone synthase gene polymorphism and the adrenocortical function in males. J Intern Med 244:11-18
202. Soro A, Ingram MC, Tonolo G, Glorioso N, Fraser R 1995 Mildly raised corticosterone excretion rates in patients with essential hypertension. J Hum Hypertens 9:391-393
203. Ganapathipillai S, Laval G, Hoffmann IS, Castejon AM, Nicod J, Dick B, Frey FJ, Frey BM, Cubeddu LX, Ferrari P 2005 CYP11B2-CYP11B1 haplotypes associated with decreased 11β-hydroxylase activity. J Clin Endocrinol Metab 90:1220-1225
204. Davies E, Holloway CD, Ingram MC, Friel EC, Inglis GC, Swan L, Hillis WS, Fraser R, Connell JMC 2001 An influence of variation in the aldosterone synthase gene (CYP11B2) on corticosteroid responses to ACTH in normal human subjects. Clin Endocrinol (Oxf) 54:813-817
205. Barr M, MacKenzie SM, Friel EC, Holloway CD, Wilkinson DM, Brain NJ, Ingram MC, Fraser R, Brown M, Samani NJ, Caulfield M, Munroe PB, Farrall M, Webster J, Clayton D, Dominiczak AF, Connell JM, Davies E 2007 Polymorphic variation in the 11β-hydroxylase gene associates with reduced 11-hydroxylase efficiency. Hypertension 49:113-119
206. Cherradi N, Brandenburger Y, Capponi AM 1998 Mitochondrial regulation of mineralocorticoid biosynthesis by calcium and StAR protein. Eur J Endocrinol 139:249-256
207. Oelkers W 1985 Prolonged ACTH infusion suppresses aldosterone secretion in spite of high renin activity. Acta Endocrinol 108:91-97
208. Tucci JR, Espiner EA, Jagger PI, Pauk GL, Lauler DP 1967 ACTH stimulation of aldosterone secretion in normal subjects and in patients with chronic adrenocortical insufficiency. J Clin Endocrinol Metab 27:568-575
209. McDougall JG, Butkus A, Coghlan JP, Denton DA, Muller J, Oddie CJ, Robinson PM, Scoggins BA 1980 Biosynthetic ad morphological evidence for inhibition of aldosterone production following administration of ACTH to sheep. Acta Endocrinol (Copenh) 94:559-570
210. Connell JMC, Whitworth J, Davies D, Lever A, Richards A, Fraser R 1987 Effects of ACTH and cortisol administration on blood pressure, electrolyte metabolism, atrial natriuretic peptide and renal function in normal man. J Hypertens 5:425-433
211. Pratt JH, Dale SL, Melby JC 1976 The effect of administered ACTH on aldosterone metabolism and secretion. J Clin Endocrinol Metab 42:355-360
212. Kem DC, Gomez-Sanchez C, Kramer NJ, Holland OB, Higgins JR 1975 Plasma aldosterone and renin activity response to ACTH infusion in dexamethasone-suppressed normal and sodium-depleted man. J Clin Endocrinol Metab 40:116-124
213. Daidoh H, Morita H, Mune T, Murayama M, Hanafusa J, Ni H, Shibata H, Yasuda K 1995 Responses of plasma adrenocortical steroids to low dose ACTH in normal subjects. Clin Endocrinol (Oxf) 43:311-315
214. Biglieri EG, Hane S, Slaton Jr PE, Forsham PH 1963 In vivo and in vitro studies of adrenal secretions in Cushing's syndrome and primary aldosteronism. J Clin Invest 42:516-524
215. Katz FH, Romfh P, Smith JA 1975 Diurnal variation of plasma aldosterone, cortisol and renin activity in supine man. J Clin Endocrinol Metab 40:125-134
216. Schambelan M, Brust NL, Chang BC, Slater KL, Biglieri EG 1976 Circadian rhythm and effect of posture on plasma aldosterone concentration in primary aldosteronism. J Clin Endocrinol Metab 43:115-131
217. Vagnucci AH, Wong AK, Liu TS 1974 Time series analysis of hormonal patterns in human plasma. Comput Biomed Res 7:513-532
218. Griffing GT, Berelowitz B, Hudson M, Salzman R, Manson JA, Aurrechia S, Melby JC, Pedersen RC, Brownie AC 1985 Plasma immunoreactive γ melanotropin in patients with idiopathic hyperaldosteronism, aldosterone-producing adenomas, and essential hypertension. J Clin Invest 76:163-169
219. Freel EM, Ingram M, Friel EC, Fraser R, Brown M, Samani NJ, Caulfield M, Munroe P, Farrall M, Webster J, Clayton D, Dominiczak AF, Davies E, Connell JM 2007 Phenotypic consequences of variation across the aldosterone synthase and 11-β hydroxylase locus in a hypertensive cohort: data from the MRC BRIGHT Study. Clin Endocrinol (Oxf) 67:832-838
220. Wolf RL, Mendlowitz M, Roboz J, Styan GP, Kornfeld P, Weigl A 1966 Treatment of hypertension with spironolactone. Double-blind study. JAMA 198:1143-1149
221. Chapman N, Dobson J, Wilson S, Dahlof B, Sever PS, Wedel H, Poulter NR 2007 Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension 49:839-845
222. Hood SJ, Taylor KP, Ashby MJ, Brown MJ 2007 The spironolactone, amiloride, losartan, and thiazide (SALT) double-blind cross-over trial in patients with low-renin hypertension and elevated aldosterone-renin ratio. Circulation 116:268-275
223. Rocha R, Stier Jr CT, Kifor I, Ochoa-Maya MR, Rennke HG, Williams GH, Adler GK 2000 Aldosterone: a mediator of myocardial necrosis and renal arteriopathy. Endocrinology 141:3871-3878
224. Blasi ER, Rocha R, Rudolph AE, Blomme EA, Polly ML, McMahon EG 2003 Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int 63:1791-1800
225. Zhou X, Ono H, Ono Y, Frohlich ED 2004 Aldosterone antagonism ameliorates proteinuria and nephrosclerosis independent of glomerular dynamics in L-NAME/SHR model. Am J Nephrol 24:242-249
226. Guo C, Martinez-Vasquez D, Mendez GP, Toniolo MF, Yao TM, Oestreicher EM, Kikuchi T, Lapointe N, Pojoga L, Williams GH, Ricchiuti V, Adler GK 2006 Mineralocorticoid receptor antagonist reduces renal injury in rodent models of types 1 and 2 diabetes mellitus. Endocrinology 147:5363-5373
227. Weinberger MH, Roniker B, Krause SL, Weiss RJ 2002 Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. Am J Hypertens 15:709-716
228. White WB, Duprez D, St Hillaire R, Krause S, Roniker B, Kuse-Hamilton J, Weber MA 2003 Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension 41:1021-1026
229. Williams GH, Burgess E, Kolloch RE, Ruilope LM, Niegowska J, Kipnes MS, Roniker B, Patrick JL, Krause SL 2004 Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension. Am J Cardiol 93:990-996
230. Weinberger MH, White WB, Ruilope LM, MacDonald TM, Davidson RC, Roniker B, Patrick JL, Krause SL 2005 Effects of eplerenone versus losartan in patients with low-renin hypertension. Am Heart J 150:426-433
231. Flack JM, Oparil S, Pratt JH, Roniker B, Garthwaite S, Kleiman JH, Yang Y, Krause SL, Workman D, Saunders E 2003 Efficacy and tolerability of eplerenone and losartan in hypertensive black and white patients. J Am Coll Cardiol 41:1148-1155
232. Pitt B, Reichek N, Willenbrock R, Zannad F, Phillips RA, Roniker B, Kleiman J, Krause S, Burns D, Williams GH 2003 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
233. Oh BH, Mitchell J, Herron JR, Chung J, Khan M, Keefe DL 2007 Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension. J Am Coll Cardiol 49:1157-1163
234. Athyros VG, Mikhailidis DP, Kakafika AI, Tziomalos K, Karagiannis A 2007 Angiotensin II reactivation and aldosterone escape phenomena in renin-angiotensin-aldosterone system blockade: is oral renin inhibition the solution? Expert Opin Pharmacother 8:529-535
235. Menard J, Gonzalez MF, Guyene TT, Bissery A 2006 Investigation of aldosterone-synthase inhibition in rats. J Hypertens 24:1147-1155
236. Borghi C, Boschi S, Ambrosioni E, Melandri G, Branzi A, Magnani B 1993 Evidence of a partial escape of renin-angiotensin-aldosterone blockade in patients with acute myocardial infarction treated with ACE inhibitors. J Clin Pharmacol 33:40-45
237. Cicoira M, Zanolla L, Franceschini L, Rossi A, Golia G, Zeni P, Caruso B, Zardini P 2002 Relation of aldosterone "escape" despite angiotensin-converting enzyme inhibitor administration to impaired exercise capacity in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 89:403-407
238. Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, Redelmeier DA 2004 Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 351:543-551