Discovered some 50 years ago, aldosterone (ALDO) has come to be recognised as a mineralocorticoid hormone with well-known endocrine properties in epithelial cells that contribute to the pathophysiology of congestive heart failure. This includes Na + resorption at the expense of K+ excretion in classic target tissues: kidneys, colon, sweat and salivary glands. Though less well known, Mg2+ excretion is likewise enhanced by ALDO, while adrenal ALDO secretion is regulated by extracellular Mg2+ ([Mg2+ ]o). An emerging body of information has and continues to identify other endocrine actions of ALDO receptor-ligand binding. They include: promoting an efflux of cytosolic free Mg2+, or [Mg2+]i, in exchange for Na+ in such non-epithelial cells as peripheral blood mononuclear cells; its influence on endothelial cell function; and its central actions that involve regulation of cerebrospinal fluid composition produced by epithelial cells of the choroid plexus, activity of the hypothalamic paraventricular nucleus involved in Na+ appetite, Na+ and H2O excretion and sympathetic nerve activity, and the regulation of TNF-α production from central and/or peripheral sources. Extra-adrenal steroidogenesi and auto/paracrine properties of ALDO generated de novo in the cardiovasculature are now under investigation and preliminary findings suggest they contribute to tissue repair. The past decade has witnessed a revival of interest in this steroid molecule. In years to come, an even broader understanding of ALDO's contribution to the pathophysiology of congestive heart failure will undoubtedly emerge.
Tait SAS ,Tait JFThe correspondence of S.A. S. Simpson and J. F. Tait with T. Reichstein during their collaborative work on the isolation and elucidation of the structure of electrocortin (later aldosterone). Steroids1998;63:440-53.
2.
Tait JF, Tait SAS.A decade (and even more) of aldosterone and other adrenal steroids . In: Biglieri EG, Melby JC (eds.). Endocrine Hypertension. New York: Raven Press; 1990;p. 5-27.
3.
Selye H.The general adaptation syndrome and the diseases of adaptation. J Clin Endocrinol1946;6:117-230.
4.
Davis JOThe physiology of congestive heart failure. In: Hamilton WF (ed.) Handbook of Physiology. Washington, DC: American Physiological Society, 1965; p. 2071-122. 5. Davis JOMechanisms of salt and water retention in congestive heart failure. Am J Med1960;29:486-506.
5.
Kagawa CM, Cella JA, Van Arman CGAction of new steroids in blocking effects of aldosterone and deoxycorticosterone on salt. Science1957;126:1015-16.
Coppage WS, Jr., Liddle GWMode of action and clinical usefulness of aldosterone antagonists. Ann N Y Acad Sci1960; 88:815-21.
8.
Weber KT, John B.Hickam Lecture: Heart-hitting tales of salt and destruction. J Lab Clin Med2000;136:7-13.
9.
Weber KTAldosterone in congestive heart failure. N Engl J Med2001;345:1689-97.
10.
StruthersADAldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure. J Cardiac Failure1996;2:47-54.
11.
Jorde UP, Vittorio T., Katz SD, Colombo PC, Latif F., Le Jemtel THElevated plasma aldosterone levels despite complete inhibition of the vascular angiotensin-converting enzyme in chronic heart failure. Circulation2002;106:1055-7.
12.
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 Med1999;341:709-17.
13.
Lösel RM, Feuring M., Falkenstein E., Wehling M.Nongenomic effects of aldosterone: cellular aspects and clinical implications . Steroids2002;67:493-8.
14.
Swaminathan R.Disorders of magnesium metabolism. J Int Fed Clin Chem1999;11(2):10-18.
15.
Mader IJ, Iseri LTSpontaneous hypopotassemia, hypomagnesemia, alkalosis and tetany due to hypersecretion of corticosterone-like mineralocorticoid. Am J Med1955;19:976-88. 17. Milne MD, Muehrcke RC, Aird I.Primary aldosteronism . Q J Med1957;26:317-35.
16.
Cope CL, Garcia-Llaurado J.The occurrence of electrocortin in human urine. BMJ1954;1(June 5):1290-4.
17.
Foye LV, Feightmeir TVAdrenal cortical carcinoma producing solely mineralocorticoid effect . Am J Med1955;19:966-75. 20. Hellem AJPrimary aldosteronism. (Report of a case). Acta Med Scand1956;155:271-4.
18.
Eales L., Linder GCPrimary aldosteronism. Some observations on a case in a Cape Coloured woman . Q J Med1956;25: 539-55.
19.
van Buchem FSP , Doorenbos H., Elings HSPrimary aldosteronism due to adrenocortical hyperplasia.Lancet1956 ;2( Aug 18):335-7.
20.
Campbell CH , Nicolaides N., Steinbeck AWAdrenocortical tumour with hypokalæmia and flaccid muscle paralysis . Lancet1956;2:553-5.
21.
Chalmers TM , FitzGerald MG, James AH, Scarborough H.Conn's syndrome with severe hypertension . Lancet1956;1: 127-32.
22.
Horton R., Biglieri EGEffect of aldosterone on the metabolism of magnesium. J Clin Endocrinol Metab1962;22:1187-92.
23.
Conn JWAldosteronism in man. Some clinical and climatological aspects. Part II. JAMA1963;183:871-8.
24.
Zwemer RL, Sullivan RCBlood chemistry of adrenal insufficiency in cats. Endocrinology1934;18:97-106.
25.
Loeb RFEffect of sodium chloride in treatment of patients with Addison's disease .Proc Soc Exp Biol Med1933;30:808-12. 29. Loeb RF, Atchley DW, Benedict EM, Leland J.Electrolyte balance studies in adrenalectomized dogs with particular reference to the excretion of sodium. J Exp Med1933 ;57:775-92. 30. Harrop GA, Soffer LJ, Ellsworth R., Trescher JHStudies on the suprarenal cortex. III. Plasma electrolytes and electrolyte excretion during suprarenal insufficiency in the dog.JExp Med1933;58:17-38.
26.
Conway EJ, Hingerty D.The influence of adrenalectomy on muscle constituents. Biochemistry1946;40:561-8.
27.
DaVanzo JP, Crossfield HC, Swingle WWEffect of various adrenal steroids on plasma magnesium and the electrocardiogram of adrenalectomized dogs. Endocrinology1958 ;63:825-30.
28.
Hanna S., MacIntyre I.The influence of aldosterone on magnesium metabolism. Lancet1960;2(Aug 13):348-50. 34. Wester PO, Dyckner T.Diuretic treatment and magnesium losses. Acta Med Scand Suppl1981;647:145-52.
29.
Leier CV, Dei Cas L., Metra M.Clinical relevance and management of the major electrolyte abnormalities in congestive heart failure: hyponatremia, hypokalemia, and hypomagnesemia . Am Heart J1994;128:564-74. 36. Wilson JRUse of antiarrhythmic drugs with heart failure: clinical efficacy, hemodynamic results, and relation to survival. Circulation1987;75:IV64-IV73. 37. Armanini D., Strasser T., Weber PCCharacterization of aldosterone binding sites in circulating human mononuclear leukocytes. Am J Physiol1985 ;248:E388-E390.
30.
Armanini D. , Witzgall H., Wehling M., Kuhnle U., Weber PCAldosterone receptors in different types of primary hyperaldosteronism. J Clin Endocrinol Metab1987;65:101-04. 39. Armanini D., Zennaro CM, Martella L., Pratesi C., Scali M., Zampollo V.Regulation of aldosterone receptors in hypertension. Steroids1993;58:611-13.
31.
Delva P., Pastori C., Degan M., Montesi G., Brazzarola P., Lechi A.Intralymphocyte free magnesium in patients with primary aldosteronism: aldosterone and lymphocyte magnesium homeostasis. Hypertension2000;35:113-17.
32.
Wodi LA, C Ahokas RA, Sun Y.,Weber KTOxidative stress and peripheral blood mononuclear cell free cytosolic magnesium in rats treated with aldosterone/salt [abstract]. J Investig Med2003;51(suppl 1):S283.
33.
Munir A., Gerling IC, Sun Y., Ali C., Weber KTProteomic analysis of peripheral blood mononuclear cell activation in aldosterone-treated rats [abstract]. J Investig Med2003; 51(suppl 1):S283.
34.
Gerling IC, Sun Y., Ahokas RA et al. Aldosteronism. An immunostimulatory state precedes the proinflammatory/fibrogenic cardiac phenotype. Am J Physiol Heart Circ Physiol2003;285:H813-H821.
35.
IchiharaA,Suzuki H., Saruta T.Effects of magnesium on the renin-angiotensin-aldosterone system in human subjects. J Lab Clin Med1993;122:432-40.
36.
Corica F., Allegra A., Ientile R. et al. Effects of the intravenous magnesium administration on aldosterone and atrial natriuretic factor plasma concentrations. Nephron1996;73: 739-41.
37.
Cantin M.Relationship of juxtaglomerular apparatus and adrenal cortex to biochemical and extracellular fluid volume changes in magnesium deficiency. Lab Invest1970;22:558-68. 47. Ginn HE, Cade R., McCallum T., Fregley M.Aldosterone secretion in magnesium-deficient rats. Endocrinology1967;80:969-71.
38.
Solounias BM , Schwartz R.The effect of magnesium deficiency on serum aldosterone in rats fed two levels of sodium. Life Sci1975;17:1211-17.
39.
Nadler JL, Buchanan T., Natarajan R.,Antonipillai I., Bergman R., Rude R.Magnesium deficiency produces insulin resistance and increased thromboxane synthesis. Hypertension1993;21:1024-9.
40.
Laurant P., Dalle M., Berthelot A., Rayssiguier Y.Time-course of the change in blood pressure level in magnesium-deficient Wistar rats. Br J Nutr1999;82:243-51.
41.
Atarashi K. , Matsuoka H.,Takagi M., Sugimoto T.Magnesium ion: a possible physiological regulator of aldosterone production. Life Sci1989;44:1483-9.
42.
MacIntyre I. , Davidsson D.The production of secondary potassium depletion, sodium retention, nephrocalcinosis and hypercalcinemia by magnesium deficiency . Biochem J1958; 70:456-62.
43.
Madden JA, Smith GA, Llaurado JGMyocardial K kinetics in rats on Mg-deficient diet. J Am Coll Nutr1982;1:323-9.
44.
Chang C., Bloom S.Interrelationship of dietary Mg intake and electrolyte homeostasis in hamsters: I. Severe Mg deficiency, electrolyte homeostasis, and myocardial necrosis . J Am Coll Nutr1985;4:173-85.
45.
Hall CE, Hall O.Hypertension and hypersalimentation. I. Aldosterone hypertension. Lab Invest1965;14:285-94.
46.
Brilla CG, Pick R.,Tan LB, Janicki JS, Weber KTRemodeling of the rat right and left ventricle in experimental hypertension . Circ Res1990;67:1355-64.
47.
Sun Y., Ratajska A., Zhou G.,Weber KTAngiotensin converting enzyme and myocardial fibrosis in the rat receiving angiotensin II or aldosterone. J Lab Clin Med1993 ;122 :395403.
48.
Robert V., Van Thiem N., Cheav SL, Mouas C., Swynghedauw B., Delcayre C.Increased cardiac types I and III collagen mRNAs in aldosterone-salt hypertension . Hypertension1994;24:30-6. 59. Sun Y., Ramires FJA , Weber KTFibrosis of atria and great vessels in response to angiotensin II or aldosterone infusion. Cardiovasc Res1997;35:138-47. 60. Campbell SE, Janicki JS, Weber KTTemporal differences in fibroblast proliferation and phenotype expression in response to chronic administration of angiotensin II or aldosterone. J Mol Cell Cardiol1995 ;27:1545-60.
49.
Nicoletti A. , Mandet C., Challah M., Barity J., Michel J-B.Mediators of perivascular inflammation in the left ventricle of renovascular hypertensive rats. Cardiovasc Res1996;31:585-95.
50.
Fiebeler A. , Schmidt F., Müller DN et al. Mineralocorticoid receptor affects AP-1 and nuclear factor-kB activation in angiotensin II-induced cardiac injury . Hypertension2001;37: 787-93.
51.
Rocha R., Stier CT, Jr., Kifor I. et al.Aldosterone: a mediator of myocardial necrosis and renal arteriopathy . Endocrinology2000;141:3871-8.
52.
Selye H.Protection by a steroid-spironolactone against certain types of cardiac necroses . Proc Soc Exp Biol Med1960;104:212-13.
53.
Young M., Head G., Funder J.Determinants of cardiac fibrosis in experimental hypermineralocorticoid states . Am J Physiol1995;269:E657-E662.
54.
Benetos A., Lacolley P., Safar MEPrevention of aortic fibrosis by spironolactone in spontaneously hypertensive rats. Arterioscler Thromb Vasc Biol1997;17:1152-6.
55.
Lacolley P. , Safar ME, Lucet B., Ledudal K., Labat C., Benetos A.Prevention of aortic and cardiac fibrosis by spironolactone in old normotensive rats. J Am Coll Cardiol2001;37:662-7. 68. Martinez DV, Rocha R., Matsumura M. et al. Cardiac damage prevention by eplerenone: comparison with low sodium diet or potassium loading. Hypertension2002;39:614-18.
56.
Rocha R., Rudolph AE, Frierdich GE et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol2002;283:H1802-H1810.
57.
Zannad F., Alla F., Dousset B., Perez A., Pitt B.Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators . Circulation2000;102:2700-06.
58.
Thompson JS , Palmieri GM, Eliel LP, Crawford RLThe effect of porcine calcitonin on osteoporosis induced by adrenal cortical steroids. J Bone Joint Surg Am1972;54:1490-500.
59.
Sun Y., Zhang J., Lu L., Chen SS, Quinn MT, Weber KTAldosterone-induced inflammation in the rat heart. Role of oxidative stress . Am J Pathol2002;161:1773-81.
60.
MaiselA,Cesario D., Baird S., Rehman J., Haghighi P., Carter S.Experimental autoimmune myocarditis produced by adoptive transfer of splenocytes after myocardial infarction. Circ Res1998 ;82:458-63.
61.
Ryan MF, Ryan MPLymphocyte electrolyte alterations during magnesium deficiency in the rat . Ir J Med Sci1979; 148:108-09.
62.
Wiles ME, Wagner TL, Weglicki WBEffect of acute magnesium deficiency (MgD) on aortic endothelial cell (EC) oxidant production. Life Sci1997;60:221-36.
63.
Weglicki WB , Mak IT, Stafford RE, Dickens BF, Cassidy MM, Phillips TMNeurogenic peptides and the cardiomyopathy of magnesium-deficiency: effects of substance P-receptor inhibition. Mol Cell Biochem1994;130:103-09.
64.
Weglicki WB , Dickens BF, Wagner TL, Chmielinska JJ, Phillips TMImmunoregulation by neuropeptides in magnesium deficiency: ex vivo effect of enhanced substance P production on circulating T lymphocytes from magnesium-deficient mice. Magnes Res1996;9:3-11.
65.
Mak IT, Komarov AM, Wagner TL, Stafford RE, Dickens BF, Weglicki WBEnhanced NO production during Mg deficiency and its role in mediating red blood cell glutathione loss. Am J Physiol1996;271:C385-C390.
66.
Weglicki WB , Mak IT, Phillips TMBlockade of cardiac inflammation in Mg2+ deficiency by substance P receptor inhibition. Circ Res1994;74:1009-13.
67.
Felder RB, Francis J., Zhang ZH, Wei SG, Weiss RM, Johnson AKHeart failure and the brain: new perspectives. Am J Physiol2003;284:R259-R276.
68.
Anker SD, Chua TP, Ponikowski P. et al. Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation1997;96: 526-34.
69.
Taddei S., Virdis A., Mattei Salvetti A.Vasodilation to acetylcholine in primary and secondary forms of human hypertension . Hypertension1993;21:929-33.
70.
Farquharson CA, Struthers ADSpironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure. Circulation2000;101:594-7.
71.
Bauersachs J., Heck M., Fraccarollo D. et al. Addition of spironolactone to angiotensin-converting enzyme inhibition in heart failure improves endothelial vasomotor dysfunction: role of vascular superoxide anion formation and endothelial nitric oxide synthase expression. J Am Coll Cardiol2002;39:351-8. 85. Weber KT, Singh KD, Hey JCIdiopathic intracranial hypertension with primary aldosteronism. Report of two cases. Am J Med Sci2002;324:45-50.
72.
Mendonça E. , Albuquerque L., Jácombe L., Luís MLS, Rosa FCPseudotumor cerebri in a patient with Bartter's syndrome and obesity. Nephron1996;72:989.
73.
Gomez-Sanchez CE, Zhou MY, Cozza EN, Morita H., Foecking MF, Gomez-Sanchez EPAldosterone biosynthesis in the rat brain . Endocrinology1997;138:3369-73.
74.
Slight SH, Joseph J., Ganjam VK, Weber KTExtra-adrenal mineralocorticoids and cardiovascular tissue. J Mol Cell Cardiol1999;31:1175-84.
75.
Delcayre C. , Swynghedauw B.Molecular mechanisms of myocardial remodeling. The role of aldosterone. J Mol Cell Cardiol2002;34:1577-84.
76.
Birmingham MK, Sar M., Stumpf WELocalization of aldosterone and corticostorone in the central nervous system, assessed by quantitative autoradiography. Neurochem Res1984;9:333-50.
77.
Wright EMTransport processes in the formation of the cerebrospinal fluid. Rev Physiol Biochem Pharmacol1978;83: 1-34.
78.
Vates TS, Jr., Bonting SL, Oppelt WWNa-K activated adenosine triphosphatase formation of cerebrospinal fluid in the cat. Am J Physiol1964;206:1165-72.
79.
Johanson CE , Reed DJ, Woodbury DMActive transport of sodium and potassium by the choroid plexus of the rat. J Physiol1974 ;241:359-72.
80.
Loffreda N. , Eldin P., Auzou G., Frelin C., Claire M.Corticosteroid receptors in cells derived from rat brain microvessels: mRNA identification and aldosterone binding. Am J Physiol1992 ;262:C156-C163.
81.
Ames A., III, Higashi K., Nesbett FBEffects of PCO2, acetazolamide and ouabain on volume and composition of choroid-plexus fluid. J Physiol1965;181:516-24.
82.
Davson H., Segal MBThe effects of some inhibitors and accelerators of sodium transport on the turnover of 22Na in the cerebrospinal fluid and the brain. J Physiol1970;209:131-53. 97. Kageyama Y., Suzuki H., Saruta T.Presence of aldosterone-like immunoreactivity in cerebrospinal fluid in normotensive subjects. Acta Endocrinol1992;126:501-04.
83.
MasuzawaT,Saito T., Sato F.Cytochemical study on enzyme activity asociated with cerebrospinal fluid secretion in the choroid plexus and ventricular ependyma. Brain Res1981; 222:309-22.
84.
Klarr SA, Ulanski LJ, II, Stummer W., Xiang J., Betz AL, Keep RFThe effects of hypo- and hyperkalemia on choroid plexus potassium transport . Brain Res1997;758:39-44.
85.
KageyamaY,Bravo ELHypertensive mechanisms associated with centrally administered aldosterone in dogs. Hypertension1988;11:750-3.
86.
Gómez-Sánchez EPIntracerebroventricular infusion of aldosterone induces hypertension in rats. Endocrinology1986;118:819-23.
87.
Zhang ZH, Francis J., Weiss RM, Felder RBThe renin-angiotensin-aldosterone system excites hypothalamic paraventricular nucleus neurons in heart failure. Am J Physiol2002;283:H423-H433.
88.
Francis J. ,Weiss RM,Wei SG et al. Central mineralocorticoid receptor blockade improves volume regulation and reduces sympathetic drive in heart failure. Am J Physiol2001;281: H2241-H2251.
89.
Francis J. , Weiss RM, Johnson AK, Felder RBCentral mineralocorticoid receptor blockade decreases plasma TNF-α after coronary artery ligation in rats. Am J Physiol2003;284:R328-R335.
90.
Lockett MFHormonal actions of the heart and of lungs on the isolated kidney. J Physiol1967;193:661-9.
91.
Lockett MF , Retallack RWThe isolation of a substance very closely resembling the 18-monoacetate of D-aldosterone from the venous blood of activated muscle and from contracting muscle. J Physiol1969 ;204:435-42.
92.
Lockett MFChanges in the flow and composition of the urine induced by the 18 monoacetate of D-aldosterone, in cats. J Physiol1969;202:671-82.
93.
Lockett MFRetallack RWThe influence of heart rate on the secretion of a substance closely influence of heart rate on the secretion of a substance closely resembling the 18-monoacetate of D-aldosterone by the hearts of cats under chloralose anaesthesia. J Physiol1970 ;208:21-32.
94.
Lockett MF , Retallack RWFactors controlling the secretion of a substance biologically resembling the 18-monoacetate of D-aldosterone by heart muscle . J Physiol1970;210:717-25. 110. Lockett MF, Retallack RWThe isolation of a renally active substance from arterial blood. J Physiol1972;223:49-57.
95.
Takeda Y., Miyamori I., Yoneda T. et al. Production of aldosterone in isolated rat blood vessels. Hypertension1995;25:170-3. 112. Takeda Y., Miyamori I., Yoneda T. et al. Regulation of aldosterone synthase in human vascular endothelial cells by angiotensin II and adrenocorticotropin. J Clin Endocrinol Metab1996;81:2797-800.
96.
Silvestre J-S., Robert V., Heymes C. et al. Myocardial production of aldosterone and corticosterone in the rat. J Biol Chem1998;273:4883-91.
97.
Hatakeyama H., Miyamori I., Fujita T., Takeda Y., Takeda R., Yamamoto H.Vascular aldosterone. Biosynthesis and a link to angiotensin II-induced hypertrophy of vascular smooth muscle cells. JBiol Chem1994;269:24316-20.
98.
Mizuno Y., Yoshimura M., Yasue H. et al. Aldosterone production is activated in failing ventricle in humans. Circulation2001;103:72-7.
99.
Yoshimura M., Nakamura S., Ito T. et al. Expression of aldosterone synthase gene in failing human heart: quantitative analysis using modified real-time polymerase chain reaction. J Clin Endocrinol Metab2002;87:3936-40.
100.
Slight SH, Ganjam VK, Gómez-Sánchez CE, Zhou M.-Y, Weber KTHigh affinity NAD+-dependent 11 -hydroxysteroid dehydrogenase in the human heart. J Mol Cell Cardiol1996;28:781-7.
101.
Sun Y. , Cleutjens JPM, Diaz-Arias AA, Weber KTCardiac angiotensin converting enzyme and myocardial fibrosis in the rat. Cardiovasc Res1994;28:1423-32.
102.
Sun Y. ,Weber KTAngiotensin II receptor binding following myocardial infarction in the rat. Cardiovasc Res1994 ;28:1623-8.
103.
Sun Y. ,Weber KTCells expressing angiotensin II receptors in fibrous tissue of rat heart. Cardiovasc Res1996;31:518-25. 121. Passier RC, Smits JF, Verluyten MJ, Daemen MJExpression and localization of renin and angiotensinogen in rat heart after myocardial infarction . Am J Physiol1996;271:H1040-H1048. 122. Lefroy DC, Wharton J., Crake T. et al. Regional changes in angiotensin II receptor density after experimental myocardial infarction . J Mol Cell Cardiol1996;28:429-40.
104.
SunY., Zhang JQ, Zhang J., Ramires FJA.Angiotensin II, transforming growth factor- 1 and repair in the infarcted heart. J Mol Cell Cardiol1998;30:1559-69.
105.
Silvestre J-S., Heymes C., Oubénaïssa A. et al. Activation of cardiac aldosterone production in rat myocardial infarction. Effect of angiotensin II receptor blockade and role in cardiac fibrosis. Circulation1999 ;99:2694-701.
106.
Delcayre C. , Silvestre JS, Garnier A. et al. Cardiac aldosterone production and ventricular remodeling. Kidney Int2000;57:1346-51.
107.
Hayashi M., Tsutamoto T., Wada A. et al. Relationship between transcardiac extraction of aldosterone and left ventricular remodeling in patients with first acute myocardial infarction: extracting aldosterone through the heart promotes ventricular remodeling after acute myocardial infarction. J Am Coll Cardiol2001;38:1375-82.
108.
Tsutamoto T. , Wada A., Maeda K. et al. Spironolactone inhibits the transcardiac extraction of aldosterone in patients with congestive heart failure. J Am Coll Cardiol2000;36:838-44.
109.
Van Belle E., Bauters C., Wernert N. et al. Neointimal thickening after balloon denudation is enhanced by aldosterone and inhibited by spironolactone, and aldosterone antagonist. Cardiovasc Res1995 ;29:27-32.
110.
Slight SH, Chilakamarri VK, Nasr S. et al. Inhibition of tissue repair by spironolactone: role of mineralocorticoids in fibrous tissue formation. Mol Cell Biochem1998;189:47-54.
111.
Rocha R., Chander PN, Khanna K., ZuckermanA., Stier CT, Jr.Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats. Hypertension1998;31(part 2):451-8. 131. Weber KTAldosteronism revisited. Perspectives on less well-recognized actions of aldosterone . J Lab Clin Med2003:142:71-82.
