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.

Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Wehling M: Specific, nongenomic actions of steroid hormones. Annu Rev Physiol 1997;59:365–393.
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.
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.
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.
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.
Rajagopalan S, Duquaine D, King S, Pitt B, Patel P: Mineralocorticoid receptor antagonism in experimental atherosclerosis. Circulation 2002;105:2212–2216.
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.
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.
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.
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.
Romagni P, Rossi F, Guerrini L, Quirini C, Santiemma V: Aldosterone induces contraction of the resistance arteries in man. Atherosclerosis 2003;166:345–349.
Arora RB: Role of aldosterone in myocardial infarction. Ann NY Acad Sci 1965;118:539–554.
Hene RJ, Boer P, Koomans HA, Mees EJ: Plasma aldosterone concentrations in chronic renal disease. Kidney Int 1982;21:98–101.
Sato A, Hayashi K, Naruse M, Saruta T: Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension 2003;41:64–68.
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.
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.
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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