Progress in Cardiovascular Diseases
Volume 52, Issue 5 , Pages 393-400 , March 2010

Aldosterone and Mineralocorticoid Receptors in the Cardiovascular System

  • John W. Funder

      Affiliations

    • Corresponding Author InformationAddress reprint requests to John W. Funder, Prince Henry's Institute of Medical Research, Monash Medical Centre, Clayton, Victoria 3168, Australia.

References 

  1. Crabbe J. Stimulation of active sodium transport by the isolated toad bladder with aldosterone in vitro. J Clin Invest. 1961;40:2103–2110
  2. Davis JO, Carpenter CC, Ayers CR, et al. Evidence for a secretion of an aldosterone stimulating hormone from the kidney. J Clin Invest. 1961;40:684–696
  3. Davis JO, Hartroft PM, Tins DO, et al. The role of the renin angiotensin system in the control of aldosterone secretion. J Clin Invest. 1962;41:378–389
  4. Mangelsdorf DJ, Thummel C, Beato M, et al. The nuclear receptor superfamily: the second decade. Cell. 1995;83:835–839
  5. Funder JW. The nongenomic actions of aldosterone. Endocr Rev. 2005;26:313–321
  6. Krozowski ZS, Funder JW. Renal mineralocorticoid receptors and hippocampal corticosterone-binding species have identical intrinsic steroid specificity. Proc Natl Acad Sci U S A. 1983;80:6056–6060
  7. Pearce P, Funder JW. High affinity aldosterone binding sites (type 1 receptors) in rat heart. Clin Exp Pharmacol Physiol. 1987;14:859–866
  8. Funder JW, Myles K. Exclusion of corticosterone from epithelial mineralocorticoid receptors is insufficient for selectivity of aldosterone action: in vivo binding studies. Endocrinol. 1996;137:5264–5268
  9. Funder JW, Pearce P, Smith R, et al. Mineralocorticoid action: target-tissue specificity is enzyme, not receptor, mediated. Science. 1988;242:583–585
  10. Edwards CR, Stewart PM, Burt D, et al. Localisation of 11 beta-hydroxysteroid dehydrogenase - tissue specific protector of the mineralocorticoid receptor. Lancet. 1988;2:986–989
  11. Funder JW, Pearce PT, Smith R, et al. Vascular type I aldosterone binding sites are physiological mineralocorticoid receptors. Endocrinology. 1989;125:2224–2226
  12. Conn J. Primary aldosteronism: a new clinical syndrome. J Lab Clin Med. 1955;45:3–17
  13. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341:709–717
  14. Okubo S, Niimura F, Nishimura H, et al. Angiotensin-independent mechanism for aldosterone synthesis during chronic extracellular fluid volume depletion. J Clin Invest. 1997;99:855–860
  15. Romagni P, Rossi F, Guerrini L, et al. Aldosterone induces contraction of the resistance arteries in man. Atherosclerosis. 2003;166:345–349
  16. Levy D, Rocha R, Funder JW. Distinguishing the antihypertensive and electrolyte effects of eplerenone. J Clin Endocrinol Metab. 2004;89:2736–2740
  17. Gomez-Sanchez EP. What is the role of the central nervous system in mineralocorticoid hypertension. Am J Hyperten. 1991;4:374–381
  18. Gomez-Sanchez EP, Venkataraman MT, Thwaites D, et al. ICV infusion of corticosterone antagonizes ICV-aldosterone hypertension. Am J Physiol. 1990;258(4 Pt 1):E649–E653
  19. Gomez-Sanchez EP, Fort CM, Gomez-Sanchez CE. Intracerebroventricular infusion of RU28318 blocks aldosterone-salt hypertension. Am J Physiol. 1990;258(3 Pt 1):E482–E484
  20. Gomez-Sanchez EP, Fort C, Thwaites D. Central mineralocorticoid receptor antagonism blocks hypertension in Dahl S/JR rats. Am J Physiol. 1992;262(1 Pt 1):E96–E99
  21. Gomez-Sanchez E, Samuel J, Vergaza G, et al. Effect of 3beta hydroxysteroid dehydrogenase inhibition by trilostane on blood pressure in the Dahl salt sensitive rat. Am J Physiol. 2004;this issue
  22. Huang BS, White RA, Jeng AY, et al: 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 (First published December 31, 2008), doi:10.1152/ajpregu.90903.2008.
  23. Funder JW. How do central mineralocorticoid receptors modulate blood pressure?. Am J Physiol. 2005;288:R356–R357
  24. Funder JW. Editorial focus. Trilostane, FAD286, and the role of aldosterone in the central regulation of blood pressure: focus on “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. 2009;296:R992–R993
  25. Rahmouni K, Barthelmebs M, Grima M, et al. Influence of sodium intake on the cardiovascular and renal effects of brain mineralocorticoid receptor blockade in normotensive rats. J Hypertens. 2002;20:1829–1834
  26. Funder JW, Carey RM, Fardella C, et al. Case detection, diagnosis and treatment of patients with primary aldosteronism. J Clin Endocrinol Metab. 2008;3266–3281
  27. Calhoun DA, Nishizaka MK, et al. Aldosterone secretion among patients with resistant hypertension and symptoms of sleep apnea. CHEST. 2004;125:112–117
  28. Milliez P, Girerd X, Plouin P-F, et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005;45:1243–1248
  29. Stowasser M, Sharman J, Leano R, et al. Evidence for abnormal left ventricular structure and function in normotensive individuals with familial hyperaldosteronism type I. J Clin Endocrinol Metab. 2005;90:5070–5076
  30. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309–1321
  31. Epstein M, Buckalew V, Martinez FJ, et al. Antiproteinuric efficacy of eplerenone, enalapril and eplerenone/enalapril combination in diabetic hypertensives with microalbuminuria. Am J Hypertens. 2002;24A:15;(abstract)
  32. Epstein M, Alexander JC, Roniker B. Eplerenone, a new selective aldosterone receptor antagonist (SARA): efficacy in patients with mild to moderate hypertension. J Am Soc Nephrol. 1998;9:A1640
  33. Guder G, Bauersachs J, Frantz S, et al. Complementary and incremental mortality risk prediction by cortisol and aldosterone in chronic heart failure. Circulation. 2007;115:1754–1761
  34. Qin W, Rudolph A, Bond B, et al. A transgenic model of aldosterone-driven cardiac hypertrophy and heart failure. Circ Res. 2003;93:69–76
  35. In:  Mihailidou AS,  Mardini M,  Fraser T,  Knights D,  Funder JW editor. Agonist/antagonist activity of cortisol in cardiomyocyte mineralocorticoid receptors is determined by redox state. 30th Annual Meeting of the International Aldosterone Conference. June 14-15, 2004;New Orleans, LA
  36. Funder JW. Is aldosterone bad for the heart?. Trends Endocrinol Metab. 2004;15:139–142
  37. Ward MR, Kanellakis P, Ramsey D, et al. Eplerenone suppresses constrictive remodeling and collagen accumulation after angioplasty in porcine coronary arteries. Circulation. 2001;104:467–472
  38. Mihailidou AS, Loan Le TY, Mardini M, et al. Glucocorticoids activate cardiac mineralocorticoid receptors during experimental myocardial infarction. Hypertension. 2009;54:1306–1312
  39. Fjeld C, Birdsong W, Goodman R. Differential binding of NAD+ and NADH allows the transcriptional corepressor carboxyl-terminal binding protein to serve as a metabolic sensor. Proc Natl Acad Sci U S A. 2003;100:9202–9207
  40. Funder JW. RALES, EPHESUS and redox. J Steroid Biochem Mol Biol. 2005;93:121–125
  41. Young MJ, Funder JW. Eplerenone, but not steroid withdrawal, reverses cardiac fibrosis in DOC/salt rats. Endocrinol. 2004;145:3153–3157
  42. Kendar S, Hayek T, Kaplan M, et al. Effect of eplerenone, a selective aldosterone blocker, on the blood pressure, serum and macrophage oxidative stress, and atherosclerosis in apoprotein E-deficient mice. J Cardiovasc Pharmacol. 2003;41:955–963
  43. Rajagopalan S, Duquaine D, King S, et al. Mineralocorticoid receptor antagonism in experimental atherosclerosis. Circulation. 2002;105:2212–2216
  44. Takai S, Musamabu M, Kirimura K, et al. Eplerenone inhibits atherosclerosis in nonhuman primates. Hypertension. 2005;46:1135–1139

PII: S0033-0620(09)00119-4

doi: 10.1016/j.pcad.2009.12.003

Progress in Cardiovascular Diseases
Volume 52, Issue 5 , Pages 393-400 , March 2010

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