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Endocrinology Vol. 141, No. 10 3871-3878
Copyright © 2000 by The Endocrine Society

ARTICLES

Aldosterone: A Mediator of Myocardial Necrosis and Renal Arteriopathy1

Ricardo Rocha2, Charles T. Stier, Jr., Imre Kifor, Margarita R. Ochoa-Maya, Helmut G. Rennke, Gordon H. Williams and Gail K. Adler

Departments of Medicine (R.R., I.K., M.R.O.-M., G.H.W., G.K.A.) and Pathology (H.G.R.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115; and Department of Pharmacology, New York Medical College (C.T.S.), Valhalla, New York 10595

Address all correspondence and requests for reprints to: Gail K. Adler, M.D., Ph.D., Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115. E-mail: gadler{at}partners.org

To determine the role of aldosterone in mediating cardiovascular damage, we performed ablation/replacement experiments with aldosterone in a rat model of cardiac injury. Administration of angiotensin II and N{omega}-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthesis inhibitor) to male rats drinking 1% saline caused hypertension, severe biventricular myocardial necrosis, proteinuria, and fibrinoid necrosis of renal and cardiac vessels. Removal of aldosterone by adrenalectomy or through administration of the selective aldosterone antagonist eplerenone markedly reduced the cardiac and renal damage without significantly altering blood pressure. Aldosterone infusion in adrenalectomized, glucocorticoid-replaced L-NAME/angiotensin II-treated animals restored damage. Thus, we identified aldosterone as a critical mediator of L-NAME/angiotensine II induced vascular damage through mechanisms apparently independent of its effects on systolic blood pressure.




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 Circ. Res.Home page
R. A. Ahokas, K. J. Warrington, I. C. Gerling, Y. Sun, L. A. Wodi, P. A. Herring, L. Lu, S. K. Bhattacharya, A. E. Postlethwaite, and K. T. Weber
Aldosteronism and Peripheral Blood Mononuclear Cell Activation: A Neuroendocrine-Immune Interface
Circ. Res., November 14, 2003; 93 (10): e124 - e135.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
B. Pitt, N. Reichek, R. Willenbrock, F. Zannad, R. A. Phillips, B. Roniker, J. Kleiman, S. Krause, D. Burns, and G. H. Williams
Effects of Eplerenone, Enalapril, and Eplerenone/Enalapril in Patients With Essential Hypertension and Left Ventricular Hypertrophy: The 4E-Left Ventricular Hypertrophy Study
Circulation, October 14, 2003; 108(15): 1831 - 1838.
[Abstract] [Full Text] [PDF]

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 Journal of Renin-Angiotensin-Aldosterone SystemHome page
K. T Weber, Yao Sun, L. A Wodi, A. Munir, E. Jahangir, R. A Ahokas, I. C Gerling, A. E Postlethwaite, and K. J Warrington
Toward a broader understanding of aldosterone in congestive heart failure
Journal of Renin-Angiotensin-Aldosterone System, September 1, 2003; 4(3): 155 - 163.
[Abstract] [PDF]

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 J. Am. Soc. Nephrol.Home page
S. Arima, K. Kohagura, H.-L. Xu, A. Sugawara, T. Abe, F. Satoh, K. Takeuchi, and S. Ito
Nongenomic Vascular Action of Aldosterone in the Glomerular Microcirculation
J. Am. Soc. Nephrol., September 1, 2003; 14(9): 2255 - 2263.
[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
T. H. Hostetter and H. N. Ibrahim
Aldosterone in Chronic Kidney and Cardiac Disease
J. Am. Soc. Nephrol., September 1, 2003; 14(9): 2395 - 2401.
[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
P. N. Chander, R. Rocha, J. Ranaudo, G. Singh, A. Zuckerman, and C. T. Stier Jr.
Aldosterone Plays a Pivotal Role in the Pathogenesis of Thrombotic Microangiopathy in SHRSP
J. Am. Soc. Nephrol., August 1, 2003; 14(8): 1990 - 1997.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
I. C. Gerling, Y. Sun, R. A. Ahokas, L. A. Wodi, S. K. Bhattacharya, K. J. Warrington, A. E. Postlethwaite, and K. T. Weber
Aldosteronism: an immunostimulatory state precedes proinflammatory/fibrogenic cardiac phenotype
Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H813 - H821.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
C. T. Stier Jr., P. N. Chander, L. Rosenfeld, and C. A. Powers
Estrogen promotes microvascular pathology in female stroke-prone spontaneously hypertensive rats
Am J Physiol Endocrinol Metab, July 1, 2003; 285(1): E232 - E239.
[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
J. M. Flack, R. Peters, T. Shafi, H. Alrefai, S. A. Nasser, and E. Crook
Prevention of Hypertension and Its Complications: Theoretical Basis and Guidelines for Treatment
J. Am. Soc. Nephrol., July 1, 2003; 14(90002): S92 - 98.
[Abstract] [Full Text] [PDF]

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 Arch Intern MedHome page
H. T. Yu
Progression of Chronic Renal Failure
Arch Intern Med, June 23, 2003; 163(12): 1417 - 1429.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. S. Williams and G. H. Williams
50th Anniversary of Aldosterone
J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2364 - 2372.
[Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
P. C. White
Aldosterone: Direct Effects on and Production by the Heart
J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2376 - 2383.
[Full Text] [PDF]

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 CirculationHome page
N. J. Brown
Eplerenone: Cardiovascular Protection
Circulation, May 20, 2003; 107(19): 2512 - 2518.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
T.-Y. Chun, L. J. Bloem, and J. H. Pratt
Aldosterone Inhibits Inducible Nitric Oxide Synthase in Neonatal Rat Cardiomyocytes
Endocrinology, May 1, 2003; 144(5): 1712 - 1717.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
A. J. Casal, J.-S. Silvestre, C. Delcayre, and A. M. Capponi
Expression and Modulation of Steroidogenic Acute Regulatory Protein Messenger Ribonucleic Acid in Rat Cardiocytes and after Myocardial Infarction
Endocrinology, May 1, 2003; 144(5): 1861 - 1868.
[Abstract] [Full Text] [PDF]

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 J. Med. Genet.Home page
J Song, I Narita, S Goto, N Saito, K Omori, F Sato, J Ajiro, D Saga, D Kondo, M Sakatsume, et al.
Gender specific association of aldosterone synthase gene polymorphism with renal survival in patients with IgA nephropathy
J. Med. Genet., May 1, 2003; 40(5): 372 - 376.
[Full Text] [PDF]

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 J Am Coll CardiolHome page
J. M. Flack, S. Oparil, J. H. Pratt, B. Roniker, S. Garthwaite, J. H. Kleiman, Y. Yang, S. L. Krause, D. Workman, and E. Saunders
Efficacy and tolerability of eplerenone and losartan in hypertensive black and white patients
J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1148 - 1155.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
R. Alzamora, E. T. Marusic, M. Gonzalez, and L. Michea
Nongenomic Effect of Aldosterone on Na+,K+-Adenosine Triphosphatase in Arterial Vessels
Endocrinology, April 1, 2003; 144(4): 1266 - 1272.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
M. J. Young, L. Moussa, R. Dilley, and J. W. Funder
Early Inflammatory Responses in Experimental Cardiac Hypertrophy and Fibrosis: Effects of 11{beta}-Hydroxysteroid Dehydrogenase Inactivation
Endocrinology, March 1, 2003; 144(3): 1121 - 1125.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
S. I. McFarlane and J. R. Sowers
Aldosterone Function in Diabetes Mellitus: Effects on Cardiovascular and Renal Disease
J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 516 - 523.
[Full Text] [PDF]

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 HypertensionHome page
A. Sato, K. Hayashi, M. Naruse, and T. Saruta
Effectiveness of Aldosterone Blockade in Patients With Diabetic Nephropathy
Hypertension, January 1, 2003; 41(1): 64 - 68.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
R. Rocha, C. L. Martin-Berger, P. Yang, R. Scherrer, J. Delyani, and E. McMahon
Selective Aldosterone Blockade Prevents Angiotensin II/Salt-Induced Vascular Inflammation in the Rat Heart
Endocrinology, December 1, 2002; 143(12): 4828 - 4836.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
R. Rocha, A. E. Rudolph, G. E. Frierdich, D. A. Nachowiak, B. K. Kekec, E. A. G. Blomme, E. G. McMahon, and J. A. Delyani
Aldosterone induces a vascular inflammatory phenotype in the rat heart
Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1802 - H1810.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
H. Krum, H. Nolly, D. Workman, W. He, B. Roniker, S. Krause, and K. Fakouhi
Efficacy of Eplerenone Added to Renin-Angiotensin Blockade in Hypertensive Patients
Hypertension, August 1, 2002; 40(2): 117 - 123.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
N. Yamamoto, H. Yasue, Y. Mizuno, M. Yoshimura, H. Fujii, M. Nakayama, E. Harada, S. Nakamura, T. Ito, and H. Ogawa
Aldosterone Is Produced From Ventricles in Patients With Essential Hypertension
Hypertension, May 1, 2002; 39(5): 958 - 962.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
A. K.L. Banes and S. W. Watts
Upregulation of Arterial Serotonin 1B and 2B Receptors in Deoxycorticosterone Acetate-Salt Hypertension
Hypertension, February 1, 2002; 39(2): 394 - 398.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
C. E. Gomez-Sanchez and E. P. Gomez-Sanchez
Cardiac Steroidogenesis--New Sites of Synthesis, or Much Ado About Nothing?
J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5118 - 5120.
[Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
M. J. Young, C. D. Clyne, T. J. Cole, and J. W. Funder
Cardiac Steroidogenesis in the Normal and Failing Heart
J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5121 - 5126.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
J. H. Pratt, G. J. Eckert, S. Newman, and W. T. Ambrosius
Blood Pressure Responses to Small Doses of Amiloride and Spironolactone in Normotensive Subjects
Hypertension, November 1, 2001; 38(5): 1124 - 1129.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
M. R. Ward, P. Kanellakis, D. Ramsey, J. Funder, and A. Bobik
Eplerenone Suppresses Constrictive Remodeling and Collagen Accumulation After Angioplasty in Porcine Coronary Arteries
Circulation, July 24, 2001; 104(4): 467 - 472.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
P. N. Hopkins, S. C. Hunt, X. Jeunemaitre, B. Smith, D. Solorio, N. D.L. Fisher, N. K. Hollenberg, and G. H. Williams
Angiotensinogen Genotype Affects Renal and Adrenal Responses to Angiotensin II in Essential Hypertension
Circulation, April 23, 2002; 105(16): 1921 - 1927.
[Abstract] [Full Text] [PDF]


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