Genomic and non-genomic effects of aldosterone

Current Signal Transduction Therapy

Volumn 7, Issue 2, 2012, Pages 132-141

  Verhovez, Andrea ^a   Williams, Tracy A ^a   Monticone, Silvia ^a   Crudo, Valentina ^a   Burrello, Jacopo ^a   Galmozzi, Maddalena ^a   Covella, Michele ^a   Veglio, Franco ^a   Mulatero, Paolo ^a  

^a UNIVERSITY OF TURIN   (Italy)

Author keywords

Aldosterone; Endothelium; Hyperaldosteronism

Indexed keywords

ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); ALDOSTERONE; ANGIOTENSIN 2 RECEPTOR ANTAGONIST; CAPTOPRIL; CARBENOXOLONE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENDOTHELIAL NITRIC OXIDE SYNTHASE; EPLERENONE; HEAT SHOCK PROTEIN; INTERCELLULAR ADHESION MOLECULE 1; MINERALOCORTICOID RECEPTOR; PHOSPHOPROTEIN PHOSPHATASE 2A; PROTEIN KINASE C; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SERUM AND GLUCOCORTICOID REGULATED KINASE 1; SPIRONOLACTONE;

ARTICLE; GENE EXPRESSION REGULATION; GENOMICS; HEART DISEASE; HUMAN; HYPERTENSION; KIDNEY DISEASE; MOLECULAR BIOLOGY; MOLECULAR GENETICS; MOLECULAR PATHOLOGY; MOLECULAR RECOGNITION; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEINURIA; RENOVASCULAR HYPERTENSION; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; VASCULAR DISEASE; VASCULAR ENDOTHELIUM; VASCULAR SMOOTH MUSCLE;

EID: 84861922140     PISSN: 15743624     EISSN: None     Source Type: Journal    
DOI: 10.2174/157436212800376708     Document Type: Article

References (134)

1. Simpson SA, Tait JF, Wettstein A, Neher R, Von Euw J, Reichstein T. Isolation from the adrenals of a new crystalline hormone with especially high effectiveness on mineral metabolism. Experientia 1953; 9: 333-5.
2. Simpson SA, Tait JF. The nature of the circulating hormones of the adrenal cortex in man. Arch Middx Hosp 1953; 3: 209-18.
3. Crabbe J. Stimulation of active sodium transport by the isolated toad bladder with aldosterone in vitro. J Clin Invest 1961; 40: 2103-10.
4. Ogishima T, Suzuki H, Hata J, Mitani F, Ishimura Y. Zone-specific expression of aldosterone synthase cytochrome P-450 and cytochrome P-45011 beta in rat adrenal cortex: histochemical basis for the functional zonation. Endocrinology 1992; 130: 2971-7.
5. Denner K, Doehmer J, Bernhardt R. Cloning of CYP11B1 and CYP11B2 from normal human adrenal and their functional expression in COS-7 and V79 Chinese hamster cells. Endocr Res 1995; 21: 443-8.
6. Spat A. Glomerulosa cell-a unique sensor of extracellular K concentration. Mol Cell Endocrinol 2004; 217: 23-6. (Pubitemid 38596624)
7. Bassett MH, White PC, Rainey WE. The regulation of aldosterone synthase expression. Mol Cell Endocrinol 2004; 217: 67-74. (Pubitemid 38596630)
8. Waterman MR, Bischof LJ. Cytochromes P450 12: diversity of ACTH (cAMP)-dependent transcription of bovine steroid hydroxylase genes. FASEB J 1997; 11: 419-27. (Pubitemid 27259983)
9. Holland OB, Carr B. Modulation of aldosterone synthase messenger ribonucleic acid levels by dietary sodium and potassium and by adrenocorticotropin. Endocrinology 1993; 132: 2666-73. (Pubitemid 23156925)
10. Willenberg HS, Schinner S, Ansurudeen I. New mechanisms to control aldosterone synthesis. Horm Metab Res 2008; 40: 435-41.
11. Mangelsdorf DJ, Thummel C, Beato M, et al. The nuclear receptor superfamily: the second decade. Cell 1995; 83: 835-9.
12. Evans RM. The steroid and thyroid hormone receptor superfamily. Science 1988; 240: 889-95.
13. Rogerson FM, Brennan FE, Fuller PJ. Mineralocorticoid receptor binding, structure and function. Mol Cell Endocrinol 2004; 217: 203-12. (Pubitemid 38607410)
14. Pratt WB. The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. J Biol Chem 1993; 268: 21455-8. (Pubitemid 23320624)
15. Trapp T, Holsboer F. Ligand-induced conformational changes in the mineralocorticoid receptor analyzed by protease mapping. Biochem Biophys Res Commun 1995; 215: 286-91.
16. Fejes-Toth G, Pearce D, Naray-Fejes-Toth A. Subcellular localization of mineralocorticoid receptors in living cells: effects of receptor agonists and antagonists. Proc Natl Acad Sci USA 1998; 95: 2973-8.
17. Robert-Nicoud M, Flahaut M, Elalouf JM, et al. Transcriptome of a mouse kidney cortical collecting duct cell line: effects of aldosterone and vasopressin. Proc Natl Acad Sci USA 2001; 98: 2712-6. (Pubitemid 32209548)
18. Meijer OC, Williamson A, Dallman MF, Pearce D. Transcriptional repression of the 5-HT1A receptor promoter by corticosterone via mineralocorticoid receptors depends on the cellular context. J Neuroendocrinol 2001; 12: 245-54. (Pubitemid 30156516)
19. Arriza JL, Weinberger C, Cerelli G, et al. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science 1987; 237: 268-75. (Pubitemid 17095145)
20. Lim-Tio SS, Keightley MC, Fuller PJ. Determinants of specificity of transactivation by the mineralocorticoid or glucocorticoid receptor. Endocrinology 1997; 138: 2537-43. (Pubitemid 27215260)
21. Funder JW, Pearce PT, Smith R, Smith AI. Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science 1988; 242: 583-5. (Pubitemid 18263202)
22. Stewart PM, Corrie JE, Shackleton CH, Edwards CR. Syndrome of apparent mineralocorticoid excess. A defect in the cortisolcortisone shuttle. J Clin Invest 1988; 82: 340-9.
23. Bhargava A, Pearce D. Mechanisms of mineralocorticoid action: determinants of receptor specificity and actions of regulated gene products. Trends Endocrinol Metab 2004; 15: 147-53. (Pubitemid 38510493)
24. Verrey F. Transcriptional control of sodium transport in tight epithelial by adrenal steroids. J Membr Biol 1995; 144: 93-110.
25. Kim GH, Masilamani S, Turner R, Mitchell C, Wade JB, Knepper MA. The thiazide-sensitive Na-Cl cotransporter is an aldosteroneinduced protein. Proc Natl Acad Sci USA 1998; 95: 14552-7. (Pubitemid 28549405)
26. Cho JH, Musch MW, Bookstein CM, McSwine RL, Rabenau K, Chang EB. Aldosterone stimulates intestinal Na+ absorption in rats by increasing NHE3 expression of the proximal colon. Am J Physiol 1998; 274: C586-94.
27. Ichimura T, Yamamura H, Sasamoto K, et al. 14-3-3 Proteins modulate the expression of epithelial Na+ channels by phosphorylation-dependent interaction with Nedd4-2 ubiquitin ligase. J Biol Chem 2005; 280: 13187-94.
28. Zecevic M, Heitzmann D, Camargo SM, Verrey F. SGK1 increases Na,K-ATP cell-surface expression and function in Xenopus laevis oocytes. Pflugers Arch 2004; 448: 29-35. (Pubitemid 38657202)
29. Knight KK, Olson DR, Zhou R, Snyder PM. Liddle's syndrome mutations increase Na+ transport through dual effects on epithelial Na+ channel surface expression and proteolytic cleavage. Proc Natl Acad Sci USA 2006; 103: 2805-8.
30. Fejes-Tóth G, Frindt G, Náray-Fejes-Tóth A, Palmer LG. Epithelial Na+ channel activation and processing in mice lacking SGK1. Am J Physiol Renal Physiol 2008; 294: F1298-305.
31. Bhalla V, Soundararajan R, Pao AC, Li H, Pearce D. Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ. Am J Physiol Renal Physiol 2006; 291: F714-21. (Pubitemid 44506967)
32. Capurro C, Coutry N, Bonvalet JP, Escoubet B, Garty H, Farman N. Cellular localization and regulation of CHIF in kidney and colon. Am J Physiol 1996; 271: C753-62.
33. Garty H, Lindzen M, Füzesi M, et al. A specific functional interaction between CHIF and Na,K-ATPase: role of FXYD proteins in the cellular regulation of the pump. Ann N Y Acad Sci 2003; 986: 395-400. (Pubitemid 36584140)
34. Staruschenko A, Patel P, Tong Q, Medina JL, Stockand JD. Ras activates the epithelial Na(+) channel through phosphoinositide 3-OH kinase signaling. J Biol Chem 2004; 279: 37771-8. (Pubitemid 39195491)
35. Staruschenko A, Pochynyuk O, Vandewalle A, Bugaj V, Stockand JD. Acute regulation of the epithelial Na+ channel by phosphatidylinositide 3-OH kinase signaling in native collecting duct principal cells. J Am Soc Nephrol 2007; 18: 1652-61. (Pubitemid 46870302)
36. Blazer-Yost BL, Paunescu TG, Helman SI, Lee KD, Vlahos CJ. Phosphoinositide 3-kinase is required for aldosterone-regulated sodium reabsorption. Am J Physiol 1999; 277: C531-6. (Pubitemid 29458187)
37. Spach C, Streeten DH. Retardation of sodium exchange in dog erythrocytes by physiological concentrations of aldosterone, in vitro. J Clin Invest 1964; 43: 217-27.
38. Grossmann C, Gekle M. New aspects of rapid aldosterone signaling. Mol Cell Endocrinol 2009; 308: 53-62.
39. Gekle M, Golenhofen N, Oberleithner H, Silbernagl S. Rapid activation of Na+/H+-exchange by aldosterone in renal epithelialcells requires Ca2+ and stimulation of a plasma membrane proton conductance. Proc Natl Acad Sci USA 1996; 93: 10500-4.
40. Markos F, Healy V, Harvey BJ. Aldosterone rapidly activates Na+/H+ exchange in M-1 cortical collecting duct cells via a PKCMAPK pathway. Nephron Physiol 2005; 99: 1-9.
41. Schneider SW, Yano Y, Sumpio BE, et al. Rapid aldosteroneinduced cell volume increase of endothelial cells measured by the atomic force microscope. Cell Biol Int 1997; 21: 759-68. (Pubitemid 28454233)
42. Grossmann C, Benesic A, Krug AW, et al. Human mineralocorticoid receptor expression renders cells responsive for nongenotropic aldosterone actions. Mol Endocrinol 2005; 19: 1697-710. (Pubitemid 41007884)
43. Mihailidou AS, Mardini M, Funder JW. Rapid, nongenomic effects of aldosterone in the heart mediated by epsilon protein kinase C. Endocrinology 2004; 145: 773-80. (Pubitemid 38183820)
44. Markos F, Healy V, Harvey BJ. Aldosterone rapidly activates Na+/H+ exchange in M-1 cortical collecting duct cells via a PKCMAPK pathway. Nephron Physiol 2005; 99: 1-9.
45. Liu SL, Schmuck S, Chorazcyzewski JZ, Gros R, Feldman RD. Aldosterone regulates vascular reactivity: short-term effects mediated by phosphatidylinositol 3-kinase-dependent nitric oxide synthase activation. Circulation 2003; 108: 2400-6. (Pubitemid 37413549)
46. Haseroth K, Gerdes D, Berger S, et al. Rapid nongenomic effects of aldosterone in mineralocorticoid-receptor-knockout mice. Biochem Biophys Res Commun 1999; 266: 257-61. (Pubitemid 30028801)
47. Good DW, George T, Watts BA. Aldosterone inhibits HCO3 absorption via a nongenomic pathway in medullary thick ascending limb. Am J Physiol 2002; 283: F699-F706. (Pubitemid 35033957)
48. Le Moellic C, Ouvrard-Pascaud A, Capurro C, et al. Early nongenomic events in aldosterone action in renal collecting duct cells: PKCalpha activation, mineralocorticoid receptor phosphorylation, and cross-talk with the genomic response. J Am Soc Nephrol 2004; 15: 1145-60. (Pubitemid 38525996)
49. Michea L, Delpiano AM, Hitschfeld C, Lobos L, Lavandero S, Marusic ET. Eplerenone blocks nongenomic effects of aldosterone on the Na+/H+ exchanger, intracellular Ca2+ levels, and vasoconstriction in mesenteric resistance vessels. Endocrinology 2005; 146: 973-80. (Pubitemid 40289282)
50. Grossmann C, Benesic A, Krug AW, et al. Human mineralocorticoid receptor expression renders cells responsive for nongenotropic aldosterone actions. Mol Endocrinol 2005; 19: 1697-710. (Pubitemid 41007884)
51. Grossmann C, Freudinger R, Mildenberger S, Husse B, Gekle M. EF domains are sufficient for nongenomic mineralocorticoid receptor actions. J Biol Chem 2008; 283: 7109-16.
52. Schmidt BM, Oehmer S, Delles C, et al. Rapid nongenomic effects of aldosterone on human forearm vasculature. Hypertension 2003; 42: 156-60. (Pubitemid 36944589)
53. Schmidt BM, Sammer U, Fleischmann I, Schlaich M, Delles C, Schmieder RE. Rapid nongenomic effects of aldosterone on the renal vasculature in humans. Hypertension 2006; 47: 650-5. (Pubitemid 43740234)
54. Arima S, Kohagura K, Xu HL, et al. Endothelium-derived nitric oxide modulates vascular action of aldosterone in renal arteriole. Hypertension 2004; 43: 352-7. (Pubitemid 38174138)
55. Landmesser U, Hornig B, Drexler H. Endothelial function: a critical determinant in atherosclerosis? Circulation 2004; 109: 1127-33.
56. Behrendt D, Ganz P. Endothelial function: from vascular biology to clinical applications. Am J Cardiol 2002; 90: 40-8.
57. Robert A. Complete prevention of cerebral accidents in malignant hypertension. Circ Res 1956; 4: 527-32.
58. Darrow DC, Miller HC. The production of cardiac lesions by repeated injections of desoxycorticosterone acetate. J Clin Invest 1942; 21: 601-11.
59. Still WJ, Dennison SM. The pathogenesis of the glomerular changes in steroid-induced hypertension in the rat. Lab Invest 1969; 20: 249-60.
60. Rocha R, Chander PN, Khanna K, Zuckerman A, Stier CT Jr. Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats. Hypertension 1998; 31: 451-8.
61. Rocha R, Chander PN, Zuckerman A, Stier CT Jr. Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. Hypertension 1999; 33: 232-7. (Pubitemid 29065665)
62. Chander PN, Rocha R, Ranaudo J, Singh G, Zuckerman A, Stier CT Jr. Aldosterone plays a pivotal role in the pathogenesis of thrombotic microangiopathy in SHRSP. J Am Soc Nephrol 2003; 14: 1990-7. (Pubitemid 36909906)
63. Rocha R, Rudolph AE, Frierdich GE, et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol 2002; 283: H1802-10. (Pubitemid 35217013)
64. Rocha R, Martin-Berger CL, Yang P, Scherrer R, Delyani J, McMahon E. Selective aldosterone blockade prevents angiotensin II/salt-induced vascular inflammation in the rat heart. Endocrinology 2002; 143: 4828-36. (Pubitemid 35397623)
65. Young MJ, Moussa L, Dilley R, Funder JW. Early inflammatory responses in experimental cardiac hypertrophy and fibrosis: effects of 11 beta-hydroxysteroid dehydrogenase inactivation. Endocrinology 2003; 144: 1121-5. (Pubitemid 36262878)
66. Sugiyama T, Yoshimoto T, Tsuchiya K, et al. Aldosterone induces angiotensin converting enzyme gene expression via a JAK2-dependent pathway in rat endothelial cells. Endocrinology 2005; 146: 3900-6. (Pubitemid 41175760)
67. Sugiyama T, Yoshimoto T, Hirono Y, et al. Aldosterone increases osteopontin gene expression in rat endothelial cells. Biochem Biophys Res Commun 2005; 336: 163-7. (Pubitemid 41253417)
68. Caprio M, Newfell BG, la Sala A, et al. Functional mineralocorticoid receptors in human vascular endothelial cells regulate intercellular adhesion molecule-1 expression and promote leukocyte adhesion. Circ Res 2008; 102: 1359-67.
69. Krug AW, Kopprasch S, Ziegler CG, et al. Aldosterone rapidly induces leukocyte adhesion to endothelial cells: a new link between aldosterone and arteriosclerosis? Hypertension 2007; 50: 156-7.
70. Nagata D, Takahashi M, Sawai K, et al. Molecular mechanism of the inhibitory effect of aldosterone on endothelial NO synthase activity. Hypertension 2006; 48: 165-71. (Pubitemid 44297539)
71. Liu SL, Schmuck S, Chorazcyzewski JZ, Gros R, Feldman RD. Aldosterone regulates vascular reactivity: short-term effects mediated by phosphatidylinositol 3-kinase-dependent nitric oxide synthase activation. Circulation 2003; 108: 2400-6. (Pubitemid 37413549)
72. Mutoh A, Isshiki M, Fujita T. Aldosterone enhances ligandstimulated nitric oxide production in endothelial cells. Hypertens Res 2008; 31: 1811-20.
73. Somers MJ, Mavromatis K, Galis ZS, Harrison DG. Vascular superoxide production and vasomotor function in hypertension induced by deoxycorticosterone acetate-salt. Circulation 2000; 101: 1722-8. (Pubitemid 30196634)
74. Beswick RA, Zhang H, Marable D, Catravas JD, Hill WD, Webb RC. Long-term antioxidant administration attenuates mineralocorticoid hypertension and renal inflammatory response. Hypertension 2001; 37: 781-6. (Pubitemid 32199066)
75. Beswick RA, Dorrance AM, Leite R, Webb RC. NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat. Hypertension 2001; 38: 1107-11. (Pubitemid 34252814)
76. Iwashima F, Yoshimoto T, Minami I, Sakurada M, Hirono Y, Hirata Y. Aldosterone induces superoxide generation via Rac1 activation in endothelial cells. Endocrinology 2008; 149: 1009-14. (Pubitemid 351397957)
77. Leopold JA, Dam A, Maron BA, et al. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity. Nat Med 2007; 13: 189-97.
78. Williams TA, Verhovez A, Milan A, Veglio F, Mulatero P. Protective effect of spironolactone on endothelial cell apoptosis. Endocrinology 2006; 147: 2496-505.
79. Verhovez A, Zeoli A, Williams TA, et al. Primary aldosteronism (PA) and endothelial progenitor cell (EPC) bioavailability. Clin Endocrinol 2008; 69: 528-34.
80. Thum T, Schmitter K, Fleissner F, et al. Impairment of endothelial progenitor cell function and vascularization capacity by aldosterone in mice and humans. Eur Heart J 2011; 32: 1275-86.
81. Nishizaka MK, Zaman MA, Green SA, Renfroe KY, Calhoun DA. Impaired endothelium-dependent flow-mediated vasodilation in hypertensive subjects with hyperaldosteronism. Circulation 2004; 109: 2857-61. (Pubitemid 38780298)
82. Farquharson CAJ, Struthers AD. Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure. Circulation 2000; 101: 594-7. (Pubitemid 30094728)
83. Nietlispach F, Julius B, Schindler R, et al. Influence of acute and chronic mineralocorticoid excess on endothelial function in healthy men. Hypertension 2007; 50: 82-8. (Pubitemid 46986014)
84. Leibovitz E, Ebrahimian T, Paradis P, Schiffrin EL. Aldosterone induces arterial stiffness in absence of oxidative stress and endothelial dysfunction. J Hypertens 2009; 27: 2192-200.
85. Oberleithner H, Schneider SW, Albermann L, et al. Endothelial cell swelling by aldosterone. J Membr Biol 2003; 196: 163-72. (Pubitemid 38147195)
86. Oberleithner H. Is the vascular endothelium under the control of aldosterone? Facts and hypothesis. Pflugers Arch 2007; 454: 187-93. (Pubitemid 46525460)
87. Kusche-Vihrog K, Sobczak K, Bangel N, et al. Aldosterone and amiloride alter ENaC abundance in vascular endothelium. Pflugers Arch 2008; 455: 849-57. (Pubitemid 350265623)
88. Oberleithner H, Riethmuller C, Schillers H, MacGregor GA, de Wardener HE, Hausberg M. Plasma sodium stiffens vascular endothelium and reduces nitric oxide release. Proc Natl Acad Sci USA 2007; 104: 16281-6. (Pubitemid 350099397)
89. Xiao F, Puddefoot JR, Vinson GP. Aldosterone mediates angiotensin II-stimulated rat vascular smooth muscle cell proliferation. J Endocrinol 2000; 165: 533-6. (Pubitemid 30341103)
90. Lacolley P, Labat C, Pujol A, Delcayre C, Benetos A, Safar M. Increased carotid wall elastic modulus and fibronectin in aldosterone-salt-treated rats: effects of eplerenone. Circulation 2002; 106: 2848-53. (Pubitemid 35396986)
91. Jaffe IZ, Mendelsohn ME. Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circ Res 2005; 96: 643-50. (Pubitemid 40478331)
92. Jaffe IZ, Tintut Y, Newfell BG, Demer LL, Mendelsohn ME. Mineralocorticoid receptor activation promotes vascular cell calcification. Arterioscler Thromb Vasc Biol 2007; 27: 799-805. (Pubitemid 46606709)
93. Callera GE, Touyz RM, Tostes RC, et al. Aldosterone activates vascular p38MAP kinase and NADPH oxidase via c-Src. Hypertension 2005; 45: 773-9. (Pubitemid 40418380)
94. Callera GE, Montezano AC, Yogi A, et al. c-Src-dependent nongenomic signaling responses to aldosterone are increased in vascular myocytes from spontaneously hypertensive rats. Hypertension 2005; 46: 1032-8.
95. Maron BA, Zhang YY, Handy DE, et al. Aldosterone increases oxidant stress to impair guanylyl cyclase activity by cysteinyl thiol oxidation in vascular smooth muscle cells. J Biol Chem 2009; 284: 7665-72.
96. Mazak I, Fiebeler A, Muller DN, et al. Aldosterone potentiates angiotensin II-induced signaling in vascular smooth muscle cells. Circulation 2004; 109: 2792-800. (Pubitemid 38737927)
97. Lemarié CA, Simeone SM, Nikonova A, et al. Aldosteroneinduced activation of signaling pathways requires activity of angiotensin type 1a receptors. Circ Res 2009; 105: 852-9.
98. Montezano AC, Callera GE, Yogi A, 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 2008; 28: 1511-8.
99. Min LJ, Mogi M, Li JM, Iwanami J, Iwai M, Horiuchi M. Aldosterone and angiotensin II synergistically induce mitogenic response in vascular smooth muscle cells. Circ Res 2005; 97: 434-42. (Pubitemid 41298173)
100. Min LJ, Mogi M, Iwanami J, et al. Cross-talk between aldosterone and angiotensin II in vascular smooth muscle cell senescence. Cardiovasc Res 2007; 76: 506-16. (Pubitemid 350007454)
101. Young M, Funder JW. Eplerenone, but not steroid withdrawal, reverses cardiac fibrosis in deoxycorticosterone/salt-treated rats. Endocrinology 2004; 145: 3153-7. (Pubitemid 38829985)
102. Rocha R, Funder JW. The pathophysiology of aldosterone in the cardiovascular system. Ann N Y Acad Sci 2002; 970: 89-100. (Pubitemid 35286086)
103. Brilla CG, Pick R, Tan LB, Janicki JS, Weber KT. Remodeling of the rat right and left ventricles in experimental hypertension. Circ Res 1990; 67: 1355-64.
104. Hinglais N, Heudes D, Nicoletti A, et al. Colocalization of myocardial fibrosis and inflammatory cells in rats. Lab Invest 1994; 70: 286-94. (Pubitemid 24090112)
105. Delyani JA, Robinson EL, Rudolph AE. Effect of a selective aldosterone receptor antagonist in myocardial infarction. Am J Physiol Heart Circ Physiol 2001; 281: H647-54.
106. Suzuki G, Morita H, Mishima T, et al. Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. Circulation 2002; 106: 2967-72. (Pubitemid 35424750)
107. Kuster GM, Kotlyar E, Rude MK, et al. Mineralocorticoid receptor inhibition ameliorates the transition to myocardial failure and decreases oxidative stress and inflammation in mice with chronic pressure overload. Circulation 2005; 111: 420-7. (Pubitemid 40204425)
108. Lother A, Berger S, Gilsbach R, et al. Ablation of mineralocorticoid receptors in myocytes but not in fibroblasts preserves cardiac function. Hypertension 2011; 57: 746-54.
109. Usher MG, Duan SZ, Ivaschenko CY, et al. Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice. J Clin Invest 2010; 120: 3350-64.
110. Rickard AJ, Morgan J, Tesch G, Funder JW, Fuller PJ, Young MJ. Deletion of mineralocorticoid receptors from macrophages protects against deoxycorticosterone/salt-induced cardiac fibrosis and increased blood pressure. Hypertension 2009; 54: 537-43.
111. Stockand JD, Meszaros JG. Aldosterone stimulates proliferation of cardiac fibroblasts by activating Ki-RasA and MAPK1/2 signaling. Am J Physiol Heart Circ Physiol 2003; 284: H176-84. (Pubitemid 36076284)
112. Bunda S, Wang Y, Mitts TF, et al. Aldosterone Stimulates Elastogenesis in Cardiac fibroblasts via mineralocorticoid receptorindependent action involving the consecutive activation of G13, c-Src, the insulin-like growth factor-I receptor, and phosphatidylinositol 3-kinase/Akt. J Biol Chem 2009; 284: 16633-47.
113. Tsybouleva N, Zhang L, Chen S, et al. Aldosterone, through novel signaling proteins, is a fundamental molecular bridge between the genetic defect and the cardiac phenotype of hypertrophic cardiomyopathy. Circulation 2004; 109: 1284-91. (Pubitemid 38372788)
114. Fejes-Tóth G, Náray-Fejes-Tóth A. Early aldosterone-regulated genes in cardiomyocytes: clues to cardiac remodeling? Endocrinology 2007; 148: 1502-10. (Pubitemid 46457129)
115. Latouche C, Sainte-Marie Y, Steenman M, et al. Molecular signature of mineralocorticoid receptor signaling in cardiomyocytes: from cultured cells to mouse heart. Endocrinology 2010; 151: 4467-76.
116. Qin W, Rudolph AE, Bond BR, et al. Transgenic model of aldosterone-driven cardiac hypertrophy and heart failure. Circ Res 2003; 93: 69-76. (Pubitemid 36859043)
117. 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: 709-17. (Pubitemid 29407370)
118. 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: 425-31. (Pubitemid 41040281)
119. Mihailidou AS, Bundgaard H, Mardini M, Hansen PS, Kjeldsen K, Rasmussen HH. Hyperaldosteronemia in rabbits inhibits the cardiac sarcolemmal Na(+)-K(+) pump. Circ Res 2000; 86: 37-42. (Pubitemid 30044166)
120. Caballero R, Moreno I, Gonzalez T, et al. Spironolactone and its main metabolite, canrenoic acid, block human ether-a-go-gorelated gene channels. Circulation 2003; 107: 889-95. (Pubitemid 36241049)
121. Muto T, Ueda N, Opthof T, et al. Aldosterone modulates I(f) current through gene expression in cultured neonatal rat ventricular myocytes. Am J Physiol Heart Circ Physiol 2007; 293: H2710-8. (Pubitemid 350106494)
122. Ouvrard-Pascaud A, Sainte-Marie Y, Bénitah JP, et al. Conditional mineralocorticoid receptor expression in the heart leads to lifethreatening arrhythmias. Circulation 2005; 111: 3025-33. (Pubitemid 40847778)
123. Selye H, Hall CE, Rowley EM. Malignant hypertension produced by treatment with desoxycorticosterone acetate and sodium chloride. Can Men Assoc J 1943; 49: 88-92.
124. Greene EL, Kren S, Hostetter TH. Role of aldosterone in the remnant kidney model in the rat. J Clin Invest 1996; 98: 1063-8. (Pubitemid 26293326)
125. Rocha R, Funder JW. The pathophysiology of aldosterone in the cardiovascular system. Ann N Y Acad Sci 2002; 970: 89-100. (Pubitemid 35286086)
126. Stier CT Jr, Benter IF, Ahmad S, et al. Enalapril prevents stroke and kidney dysfunction in salt-loaded stroke-prone spontaneously hypertensive rats. Hypertension 1989; 13: 115-21. (Pubitemid 19060076)
127. Stier CT Jr, Sim GJ, Mahboubi K, Shen W, Levine S. Chander PN. Prevention of stroke and hypertensive renal disease bythe angiotensin II receptor antagonist DuP 753 in salt-loaded stroke-prone SHR. In: current advances in ACE inhibition 2. MacGregor GA, Sever PS, Eds. Churchill Livingstone, London, 1991; 252-256.
128. Rocha R, Chander PN, Khanna K, Zuckerman A, Stier CT Jr. Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats. Hypertension 1998; 31: 451-8.
129. Chander PN, Rocha R, Ranaudo J, Singh G, Zuckerman A, Stier CT Jr. Aldosterone plays a pivotal role in the pathogenesis of thrombotic microangiopathy in SHRSP. J Am Soc Nephrol 2003; 14: 1990-7. (Pubitemid 36909906)
130. Blasi ER, Rocha R, Rudolph AE, Blomme EA, Polly ML, McMahon EG. Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int 2003; 63: 1791-800. (Pubitemid 36513325)
131. Nishiyama A, Yao L, Fan Y, et al. Involvement of aldosterone and mineralocorticoid receptors in rat mesangial cell proliferation and deformability. Hypertension 2005; 45: 710-6. (Pubitemid 40418370)
132. Miyata K, Rahman M, Shokoji T, et al. Aldosterone stimulates reactive oxygen species production through activation of NADPH oxidase in rat mesangial cells. J Am Soc Nephrol 2005; 16: 2906-12. (Pubitemid 44743488)
133. Nagase M, Shibata S, Yoshida S, Nagase T, Gotoda T, Fujita T. Podocyte injury underlies the glomerulopathy of Dahl salthypertensive rats and is reversed by aldosterone blocker. Hypertension 2006; 47: 1084-93. (Pubitemid 44289165)
134. Shibata S, Nagase M, Yoshida S, Kawachi H, Fujita T. Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1. Hypertension 2007; 49: 355-64. (Pubitemid 46143013)