Abstract
The mineralocorticoid receptor (MR) is expressed in many cell types throughout the body, including specific neurons, and mediates diverse functions, many of which are just now being appreciated. MR that pertain to the central modulation of cardiovascular function and health are addressed herein.
References
1.
Anderson E, Kinsell LW, et al: The treatment of Addison’s disease by the intraoral administration of desoxycorticosterone acetate tablets. J Clin Endocrinol Metab 1949;9:1324–1332.
2.
Luft R, Sjögren B: The effect of desoxycorticosterone acetate and sodium chloride on blood pressure and renal function. Acta Endocrinol (Copenh) 1949;3:56–70.
3.
Raab W, Humphreys RJ, Lepeschkin E: Potentiation of pressor effects of norepinephrine and epinephrine in man by desoxycorticosterone acetate. J Clin Invest 1950;29:1397–1404.
4.
Tait JF, Tait SAS: A steroid memoir: a decade (or more) of electrocortin (aldosterone). Steroids 1988;51:213–250.
5.
Conn JW: Primary aldosteronism, a new clinical syndrome. J Lab Clin Med 1955;45:3–7.
6.
Vanatta JC, Cottle KE: Effect of desoxycorticosterone acetate on the peripheral vascular reactivity of dogs. Am J Physiol 1955;151:119–122.
7.
Jones AW, Hart RG: Altered ion transport in aortic smooth muscle during deoxycorticosterone acetate hypertension in rats. Circ Res 1975;37:333–341.
8.
Kuhlman D, Ragan C, Ferrebee JW, Atchley DW, Loeb RF: Toxic effects of deoxycorticosterone esters in dogs. Science 1939;90:496–497.
9.
Birmingham MK, Stumpf WE, Sar M: Nuclear localization of aldosterone in rat brain cells assessed by autoradiography. Experientia 1979;35:1240–1241.
10.
Brody MJ, Varner KJ, Vasquez EC, Lewis SJ: Central nervous system and the pathogenesis of hypertension: sites and mechanisms. Hypertension 1991;18:III7–III12.
11.
Gomez-Sanchez EP: Central hypertensive effects of aldosterone. Front Neuroendocrinol 1997;18:440–462.
12.
Tanabe A, Naruse M, Naruse K, Hase M, Yoshimoto T, Tanaka M, Seki T, Demura H: Left ventricular hypertrophy is more prominent in patients with primary aldosteronism than in patients with other types of secondary hypertension. Hypertens Res 1997;20:85–90.
13.
Rossi GP, Sacchetto A, Pavan E, Scognamiglio R, Pietra M, Pessina AC: Left ventricular systolic function in primary aldosteronism and hypertension. J Hypertens 1998;16:2075–2077.
14.
Gomez-Sanchez EP: Brain mineralocorticoid receptors: orchestrators of hypertension and end-organ disease. Curr Opin Nephrol Hypertens 2004;13:191–196.
15.
Gomez-Sanchez EP: Mineralocorticoid modulation of central control of blood pressure. Steroids 1995;60:69–72.
16.
Young MJ, Funder JW: Aldosterone and the heart. Trends Endocrinol Metab 2000;11:224–226.
17.
Rocha R, Rudolph AE, Frierdich GE, Nachowiak DA, Kekec BK, Blomme EA, McMahon EG, Delyani JA: Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol 2002;283:H1802–H1810.
18.
Kurtz TW: False claims of blood pressure-independent protection by blockade of the renin angiotensin aldosterone system? Hypertension 2003;41:193–196.
19.
Quinkler M, Zehnder D, Eardley KS, Lepenies J, Howie AJ, Hughes SV, Cockwell P, Hewison M, Stewart PM: Increased expression of mineralocorticoid effector mechanisms in kidney biopsies of patients with heavy proteinuria. Circulation 2005;112:1435–1443.
20.
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;144:1121–1125.
21.
Keidar S, Kaplan M, Pavlotzky E, Coleman R, Hayek T, Hamoud S, Aviram M: Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development: a possible role for angiotensin-converting enzyme and the receptors for angiotensin II and aldosterone. Circulation 2004;109:2213–2220.
22.
Francis J, Weiss RM, Johnson AK, Felder RB: Central mineralocorticoid receptor blockade decreases plasma TNF-alpha after coronary artery ligation in rats. Am J Physiol Regul Integr Comp Physiol 2003;284:R328–R335.
23.
Francis J, Weiss RM, Wei SG, Johnson AK, Beltz TG, Zimmerman K, Felder RB: Central mineralocorticoid receptor blockade improves volume regulation and reduces sympathetic drive in heart failure. Am J Physiol Heart Circ Physiol 2001;281:H2241–H2251.
24.
Francis GS: Aldosterone inhibition and heart failure: too good to be true? Am Heart J 2001;141:1–2.
25.
Felder RB, Francis J, Zhang ZH, Wei SG, Weiss RM, Johnson AK: Heart failure and the brain: new perspectives. Am J Physiol Regul Integr Comp Physiol 2003;284:R259–R276.
26.
Arriza JW, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman DE, Evans RM: Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science 1987;237:268–275.
27.
Zennaro MC, Farman N, Bonvalet JP, Lombes M: Tissue-specific expression of alpha and beta messenger ribonucleic acid isoforms of the human mineralocorticoid receptor in normal and pathological states. J Clin Endocrinol Metab 1997;82:1345–1352.
28.
Zhou MY, Gomez-Sanchez CE, Gomez-Sanchez EP: An alternatively spliced mineralocorticoid receptor mRNA causing truncation of the steroid binding domain. Mol Cell Endocrinol 2000;159:125–131.
29.
Funder JW, Pearce PT, Smith R, Smith AI: Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science 1988;242:583–585.
30.
White PC: 11beta-hydroxysteroid dehydrogenase and its role in the syndrome of apparent mineralocorticoid excess. Am J Med Sci 2001;322:308–315.
31.
Roland BL, Li KX, Funder JW: Hybridization histochemical localization of 11 beta-hydroxysteroid dehydrogenase type 2 in rat brain. Endocrinology 1995;136:4697–4700.
32.
Geerling JC, Kawata M, Loewy AD: Aldosterone-sensitive neurons in the rat central nervous system. J Comp Neurol 2006;494:515–527.
33.
Geerling JC, Engeland WC, Kawata M, Loewy AD: Aldosterone target neurons in the nucleus tractus solitarius drive sodium appetite. J Neurosci 2006;26:411–417.
34.
Geerling JC, Loewy AD: Aldosterone-sensitive neurons in the nucleus of the solitary tract: bidirectional connections with the central nucleus of the amygdala. J Comp Neurol 2006;497:646–657.
35.
Wrange O, Yu ZY: Mineralocorticoid receptor in rat kidney and hippocampus: characterization and quantitation by isoelectric focusing. Endocrinology 1983;113:243–250.
36.
De Kloet ER, Van Acker SA, Sibug RM, Oitzl MS, Meijer OC, Rahmouni K, de Jong W: Brain mineralocorticoid receptors and centrally regulated functions. Kidney Int 2000;57:1329–1336.
37.
Engelmann M, Landgraf R, Lorscher P, Conzelmann C, Probst JC, Holsboer F, Reul JM: Downregulation of brain mineralocorticoid and glucocorticoid receptor by antisense oligodeoxynucleotide treatment fails to alter spatial navigation in rats. Eur J Pharmacol 1998;361:17–26.
38.
Gomez-Sanchez CE, Zhou MY, Cozza EN, Morita H, Eddleman FC, Gomez-Sanchez EP: Corticosteroid synthesis in the central nervous system. Endocr Res 1996;22:463–470.
39.
Gomez-Sanchez CE, Zhou MY, Cozza EN, Morita H, Foecking MF, Gomez-Sanchez EP: Aldosterone biosynthesis in the rat brain. Endocrinology 1997;138:3369–3373.
40.
Gomez-Sanchez EP, Gomez-Sanchez CE: Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone. Am J Physiol 1992;263:E1125–E1130.
41.
Gomez-Sanchez EP, Gomez-Sanchez CE: Maternal hypertension and progeny blood pressure: role of aldosterone and 11b-HSD. Hypertension 1999;33:1369–1373.
42.
Low SC, Assaad SN, Rajan V, Chapman KE, Edwards CRW, Seckl JR: Regulation of 11b-hydroxysteroid dehydrogenase by sex steroids in vivo: further evidence for the existence of a second dehydrogenase in rat kidney. J Endocrinol 1993;139:27–35.
43.
Gomez-Sanchez EP, Ganjam V, Chen YJ, Cox DL, Zhou MY, Thanigaraj S, Gomez-Sanchez CE: The sheep kidney contains a novel unidirectional, high affinity NADP+-dependent 11b-hydroxysteroid dehydrogenase (11-HSD3). Steroids 1997;62:444–450.
44.
Gomez-Sanchez EP, Gomez-Sanchez CE: First there was one, then two... why more 11b-hydroxysteroid dehydrogenases? Endocrinology 1997;138:5087–5088.
45.
Banhegyi G, Benedetti A, Fulceri R, Senesi S: Cooperativity between 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase in the lumen of the endoplasmic reticulum. J Biol Chem 2004;279:27017–27021.
46.
Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, Hewison M, Stewart PM: 11β-Hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr Rev 2004;25:831–866.
47.
Gomez-Sanchez EP, Romero DG, de Rodriguez AF, Warden MP, Krozowski Z, Gomez-Sanchez CE: Hexose-6-phosphate dehydrogenase and 11β-hydroxysteroid dehydrogenase-1 tissue distribution in the rat. Endocrinology 2008;149:525–533.
48.
Le Goascogne C, Robel P, Gouézou M, Sananes N, Baulieu E, Waterman M: Neurosteroids: cytochrome P-450scc in rat brain. Science 1987;237:1212–1215.
49.
MacKenzie SM, Clark CJ, Fraser R, Gomez-Sanchez CE, Connell JMC, Davies E: Expression of 11b-hydroxylase and aldosterone synthase genes in rat brain. J Mol Endocrinol 2000;24:321–328.
50.
Gomez-Sanchez EP, Gomez-Sanchez CE: Is aldosterone synthesized in the CNS regulated and functional? Trends Endocrinol Metab 2003;14:444–446.
51.
King SR, Manna PR, Ishii T, Syapin PJ, Ginsberg SD, Wilson K, Walsh LP, Parker KL, Stocco DM, Smith RG, Lamb DJ: An essential component in steroid synthesis, the steroidogenic acute regulatory protein, is expressed in discrete regions of the brain. J Neurosci 2002;22:10613–10620.
52.
Yu L, Romero DG, Gomez-Sanchez CE, Gomez-Sanchez EP: Steroidogenic enzyme gene expression in the human brain. Mol Cell Endocrinol 2002;190:9–17.
53.
Gomez-Sanchez EP, Ahmad N, Romero DG, Gomez-Sanchez CE: Is aldosterone synthesized within the rat brain? Am J Physiol Endocrinol Metab 2005;288:E342–E346.
54.
Gomez-Sanchez EP, Fort C, Thwaites D: Central mineralocorticoid receptor antagonism blocks hypertension in Dahl S/JR rats. Am J Physiol 1992;262:E96–E99.
55.
Gomez-Sanchez EP, Samuel J, Vergara G, Ahmad N: Effect of 3β-hydroxysteroid dehydrogenase inhibition by trilostane on blood pressure in the Dahl salt-sensitive rat. Am J Physiol Regul Integr Comp Physiol 2005;288:R389–R393.
56.
Tremblay A, Parker KL, Lehoux JG: Dietary potassium supplementation and sodium restriction stimulate aldosterone synthase but not 11b-hydroxylase P-450 messenger ribonucleic acid accumulation in rat adrenals and require angiotensin II production. Endocrinology 1992;130:3152–3158.
57.
Romero DG, Plonczynski M, Vergara GR, Gomez-Sanchez EP, Gomez-Sanchez CE: Angiotensin II early regulated genes in H295R human adrenocortical cells. Physiol Genomics 2004;19:106–116.
58.
Jo H, Yang EK, Lee WJ, Park KY, Kim HJ, Park JS: Gene expression of central and peripheral renin-angiotensin system components upon dietary sodium intake in rats. Regul Pept 1996;67:115–121.
59.
Ye P, Kenyon CJ, MacKenzie SM, Seckl JR, Fraser R, Connell JM, Davies E: Regulation of aldosterone synthase gene expression in the rat adrenal gland and central nervous system by sodium and angiotensin II. Endocrinology 2003;144:3321–3328.
60.
Felder RB, Francis J, Weiss RM, Zhang ZH, Wei SG, Johnson AK: Neurohumoral regulation in ischemia-induced heart failure: role of the forebrain. Ann NY Acad Sci 2001;940:444–453.
61.
Funder JW: The role of aldosterone and mineralocorticoid receptors in cardiovascular disease. Am J Cardiovasc Drugs 2007;7:151–157.
62.
Gomez-Sanchez EP, Venkataraman MT, Thwaites D: ICV infusion of corticosterone antagonizes ICV-aldosterone hypertension. Am J Physiol 1990;258:E649–E653.
63.
Pearce D, Naray-Fejes-Toth A, Fejes-Toth G: Determinants of subnuclear organization of mineralocorticoid receptor characterized through analysis of wild type and mutant receptors. J Biol Chem 2002;277:1451–1456.
64.
Lombes M, Farman N, Oblin ME: Immunohistochemical localization of renal mineralocorticoid receptor by using an anti-idiotypic antibody that is an internal image of aldosterone. Proc Natl Acad Sci 1990;87:1086–1088.
65.
Couette B, Fagart J, Jalaguier S, Lombes M, Souque A, Rafestin-Oblin ME: Ligand-induced conformational change in the human mineralocorticoid receptor occurs within its hetero-oligomeric structure. Biochem J 1996;315:421–427.
66.
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;95:2973–2978.
67.
Nishi M, Tanaka M, Matsuda K, Sunaguchi M, Kawata M: Visualization of glucocorticoid receptor and mineralocorticoid receptor interactions in living cells with GFP-based fluorescence resonance energy transfer. J Neurosci 2004;24:4918–4927.
68.
Trapp T, Holsboer F: Ligand-induced conformational changes in the mineralocorticoid receptor analyzed by protease mapping. Biochem Biophys Res Commun 1995;215:286–291.
69.
Trapp T, Rupprecht R, Castren M, Reul JM, Holsboer F: Heterodimerization between mineralocorticoid and glucocorticoid receptor: a new principle of glucocorticoid action in the CNS. Neuron 1994;13:1457–1462.
70.
Rupprecht R, Arriza J, Spengler D, Reul JMHM, Evans RM, Holsboer F, Damm K: Transactivation and synergistic properties of the mineralocorticoid receptor: relationship to the glucocorticoid receptor. Mol Endocrinol 1993;7:597–603.
71.
Meijer OC, Steenbergen PJ, De Kloet ER: Differential expression and regional distribution of steroid receptor coactivators SRC-1 and SRC-2 in brain and pituitary. Endocrinology 2000;141:2192–2199.
72.
Pitt B, Zannad F, Cody R, Castaigne APA, Palensky J, Wittes J: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study investigators. N Engl J Med 1999;341:709–717.
73.
Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309–1321.
74.
Hollenberg NK: Aldosterone in the development and progression of renal injury. Kidney Int 2004;66:1–9.
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2009
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