The mineralocorticoid receptor mediates the effects of aldosterone. In addition to its influence on fluid and electrolyte, aldosterone plays a role in cardiac hypertrophy, tissue fibrosis, and modulation of vascular reactivity. However, the intracellular signaling mechanisms induced by aldosterone are not fully understood. Aldosterone causes slow transcriptional and rapid non-transcriptional effects. The latter include changes in intracellular calcium, c-Jun N-terminal kinase (JNK) and extracellularly regulated kinase (ERK) phosphorylation. In addition, autocrine loops involving other molecules such as the epidermal growth factor (EGF) receptor are also important in aldosterone-induced cellular mechanisms. This short review covers in vitro and in vivo studies that have investigated the pathophysiological role of aldosterone and the mineralocorticoid receptor in the cardiovascular system.

1.
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2.
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.
3.
Bauersachs J, Fraccarollo D, Ertl G, Gretz N, Wehling M, Christ M: Striking increase of natriuresis by low-dose spironolactone in congestive heart failure only in combination with ACE inhibition: Mechanistic evidence to support RALES. Circulation 2000;102:2325–2328.
4.
Arriza JL, 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.
5.
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.
6.
Takeda Y, Miyamori I, Inaba S, Furukawa K, Hatakeyama H, Yoneda T, Mabuchi H, Takeda R: Vascular aldosterone in genetically hypertensive rats. Hypertension 1997;29:45–48.
7.
Silvestre JS, Robert V, Heymes C, Aupetit-Faisant B, Mouas C, Moalic JM, Swynghedauw B, Delcayre C: Myocardial production of aldosterone and corticosterone in the rat: Physiological regulation. J Biol Chem 1998;273:4883–4891.
8.
Haseroth K, Gerdes D, Berger S, Feuring M, Gunther A, Herbst C, Christ M, Wehling M: Rapid nongenomic effects of aldosterone in mineralocorticoid-receptor-knockout mice. Biochem Biophys Res Commun 1999;266:257–261.
9.
Harvey BJ, Doolan CM, Condliffe SB, Renard C, Alzamora R, Urbach V: Non-genomic convergent and divergent signalling of rapid responses to aldosterone and estradiol in mammalian colon. Steroids 2002;67:483–491.
10.
Oshima Y, Fujio Y, Funamoto M, Negoro S, Izumi M, Nakaoka Y, Hirota H, Yamauchi-Takihara K, Kawase I: Aldosterone augments endothelin-1-induced cardiac myocyte hypertrophy with the reinforcement of the JNK pathway. FEBS Lett 2002;524:123–126.
11.
Gekle M, Freudinger R, Mildenberger S, Silbernagl S: Aldosterone interaction with epidermal growth factor receptor signaling in MDCK cells. Am J Physiol Renal Physiol 2002;282:F669–F679.
12.
Wehling M: Specific, nongenomic actions of steroid hormones. Annu Rev Physiol 1997;59:365–393.
13.
Barbato JC, Mulrow PJ, Shapiro JI, Franco-Saenz R: Rapid effects of aldosterone and spironolactone in the isolated working rat heart. Hypertension 2002;40:130–135.
14.
Limbourg FP, Huang Z, Plumier JC, Simoncini T, Fujioka M, Tuckermann J, Schutz G, Moskowitz MA, Liao JK: Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids. J Clin Invest 2002;110:1729–1738.
15.
Simoncini T, Rabkin E, Liao JK: Molecular basis of cell membrane estrogen receptor interaction with phosphatidylinositol 3-kinase in endothelial cells. Arterioscler Thromb Vasc Biol 2003;23:198–203.
16.
Fiebeler A, Schmidt F, Muller DN, Park JK, Dechend R, Bieringer M, Shagdarsuren E, Breu V, Haller H, Luft FC: Mineralocorticoid receptor affects AP-1 and nuclear factor-kappab activation in angiotensin II-induced cardiac injury. Hypertension 2001;37:787–793.
17.
Rajagopalan S, Duquaine D, King S, Pitt B, Patel P: Mineralocorticoid receptor antagonism in experimental atherosclerosis. Circulation 2002;105:2212–2216.
18.
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;143:4828–4836.
19.
Beggah AT, Escoubet B, Puttini S, Cailmail S, Delage V, Ouvrard-Pascaud A, Bocchi B, Peuchmaur M, Delcayre C, Farman N, Jaisser F: Reversible cardiac fibrosis and heart failure induced by conditional expression of an antisense mRNA of the mineralocorticoid receptor in cardiomyocytes. Proc Natl Acad Sci USA 2002;99:7160–7165.
20.
Geller DS, Farhi A, Pinkerton N, Fradley M, Moritz M, Spitzer A, Meinke G, Tsai FT, Sigler PB, Lifton RP: Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science 2000;289:119–123.
21.
Schmidt BM, Georgens AC, Martin N, Tillmann HC, Feuring M, Christ M, Wehling M: Interaction of rapid nongenomic cardiovascular aldosterone effects with the adrenergic system. J Clin Endocrinol Metab 2001;86:761–767.
22.
Romagni P, Rossi F, Guerrini L, Quirini C, Santiemma V: Aldosterone induces contraction of the resistance arteries in man. Atherosclerosis 2003;166:345–349.
23.
Arora RB: Role of aldosterone in myocardial infarction. Ann NY Acad Sci 1965;118:539–554.
24.
Hene RJ, Boer P, Koomans HA, Mees EJ: Plasma aldosterone concentrations in chronic renal disease. Kidney Int 1982;21:98–101.
25.
Sato A, Hayashi K, Naruse M, Saruta T: Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension 2003;41:64–68.
26.
Griffin KA, Abu-Amarah I, Picken M, Bidani AK: Renoprotection by ACE inhibition or aldosterone blockade is blood pressure-dependent. Hypertension 2003;41:201–206.
27.
Mandarim-de-Lacerda CA, Pereira LMM: The effects of spironolactone monotherapy on blood pressure and myocardial remodeling in spontaneously hypertensive rats: A stereological study. J Biomed Sci 2003;10:50–57.
28.
Berger S, Bleich M, Schmid W, Greger R, Schutz G: Mineralocorticoid receptor knockout mice: Lessons on Na+ metabolism. Kidney Int 2000;57:1295–1298.
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