Abstract
With an increasingly aging population, the need for effective treatment of cardiovascular diseases (eg, heart failure, hypertension, and ischemic heart disease) cannot be overemphasized. The vital importance of mineralocorticoid receptor antagonists for treating cardiovascular conditions has only been appreciated in the last decade. The re-emergence of mineralocorticoid receptor antagonists has provided clinicians with an important tool towards complete blockade of the reninangiotensin-aldosterone axis.
Similar content being viewed by others
References and Recommended Reading
Selye H: The general adaptation syndrome and the diseases of adaptation. J Clin Endocrinol 1946, 6:117–230.
Schachter M: Aldosterone antagonism: new ideas, new drugs. Br J Cardiol 2002, 9:533–537.
Brilla CG, Pick R, Tan LB, et al.: Remodeling of the rat right and left ventricles in experimental hypertension. Circ Res 1990, 67:1355–1364.
Brilla CG, Matsubara LS, Weber KT: Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. J Mol Cell Cardiol 1993, 25:563–575.
Rocha R, Rudolph AE, Frierdich GE, et al.: Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol 2002, 283:H1802–1810.
Zannad F, Alla F, Dousset B, et al.: 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. Circulation 2000, 102:2700–2706.
Duprez DA, Bauwens FR, De Buyzere ML, et al.: Influence of arterial blood pressure and aldosterone on left ventricular hypertrophy in moderate essential hypertension. Am J Cardiol 1993, 71:17A–20A.
Swedberg K, Eneroth P, Kjekshus J, Wilhelmsen L: Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. Circulation 1990, 82:1730–1736.
Farquharson CA, Struthers AD: Aldosterone induces acute endothelial dysfunction in vivo in humans: evidence for an aldosterone-induced vasculopathy. Clin Sci (Lond) 2002, 103:425–431.
Oikawa T, Freeman M, Lo W, et al.: Modulation of plasminogen activator inhibitor-1 in vivo: a new mechanism for the anti-fibrotic effect of renin-angiotensin inhibition. Kidney Int 1997, 51:164–172.
Struthers AD: Aldosterone: cardiovascular assault. Am Heart J 2002, 144:S2–7.
Vasan RS, Evans JC, Larson MG, et al.: Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N Engl J Med 2004, 351:33–41.
Mirouze D, Zipser RD, Reynolds TB: Effect of inhibitors of prostaglandin synthesis on induced diuresis in cirrhosis. Hepatology 1983, 3:50–55.
Hollifield JW: Failure of aspirin to antagonize the antihypertensive effect of spironolactone in low-renin hypertension. South Med J 1976, 69:1034–1036.
Sungaila I, Bartle WR, Walker SE, et al.: Spironolactone pharmacokinetics and pharmacodynamics in patients with cirrhotic ascites. Gastroenterology 1992, 102:1680–1685.
Sato A, Takane H, Saruta T: High serum level of procollagen type III amino-terminal peptide contributes to the efficacy of spironolactone and angiotensin-converting enzyme inhibitor therapy on left ventricular hypertrophy in essential hypertensive patients. Hypertens Res 2001, 24:99–104.
Hayashi M, Tsutamoto T, Wada A, et al.: Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction. Circulation 2003, 107:2 559–2 565.
Macdonald JE, Kennedy N, Struthers AD: Effects of spironolactone on endothelial function, vascular angiotensin converting enzyme activity, and other prognostic markers in patients with mild heart failure already taking optimal treatment. Heart 2004, 90:765–770.
Klauber N, Browne F, Anand-Apte B, D’Amato RJ: New activity of spironolactone. Inhibition of angiogenesis in vitro and in vivo. Circulation 1996, 94:2566–2571.
Huang BS, Leenen FH: Blockade of brain mineralocorticoid receptors or Na+ channels prevents sympathetic hyperactivity and improves cardiac function in rats post-MI. Am J Physiol Heart Circ Physiol 2005, 288:H2491–2497. Epub 2004 Dec 22.
Menard RH, Guenthner TM, Kon H, Gillette JR: Studies on the destruction of adrenal and testicular cytochrome P-450 by spironolactone. Requirement for the 7alpha-thio group and evidence for the loss of the heme and apoproteins of cytochrome P-450. J Biol Chem 1979, 254:1726–1733.
Feller DR, Gerald MC: Interactions of spironolactone with hepatic microsomal drug-metabolizing enzyme systems. Biochem Pharmacol 1971, 20:1991–2000.
Buck ML: The cytochrome P450 enzyme system and its effect on drug metabolism. Pediatr Pharmacother 1997, 3:1–4. Available at: http://www.healthsystem.virginia.edu/internet/pediatrics/pharma-news/MAY97.pdf. Accessed April 12, 2006.
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 Med 1999, 341:709–717.
Jeunemaitre X, Chatellier G, Kreft-Jais C, et al.: Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol 1987, 60:820–825.
Juurlink DN, Mamdani MM, Lee DS, et al.: Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004, 351:543–551.
Greenblatt DJ, Koch-Weser J: Adverse reactions to spironolactone. A report from the Boston Collaborative Drug Surveillance Program. JAMA 1973, 225:40–43.
Hughes BR, Cunliffe WJ: Tolerance of spironolactone. Br J Dermatol 1988, 118:687–691.
Aldactone—full US prescribing information. Available at: http://www.pfizer.com/pfizer/download/uspi_aldactone.pdf. Accessed April 12, 2006.
Loube SD, Quirk RA: Breast cancer associated with administration of spironolactone [letter]. Lancet 1975, 1:1428–1429.
Lindeman RD: Hypokalemia: causes, consequences and correction. Am J Med Sci 1976, 272:5–17.
Mulatero P, Stowasser M, Loh KC, et al.: Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab 2004, 89:1045–1050.
Calhoun DA, Nishizaka MK, Zaman MA, et al.: Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 2002, 40:892–896.
Lim PO, Jung RT, MacDonald TM: Raised aldosterone to renin ratio predicts antihypertensive efficacy of spironolactone: a prospective cohort follow-up study. Br J Clin Pharmacol 1999, 48:756–760.
Traina M, Vizzini GB: Controlled study of the effect of long-term administration of canrenoate potassium in cirrhotic ascites [in Italian]. Minerva Med 1986, 77:87–91.
de Gasparo M, Joss U, Ramjoue HP, et al.: Three new epoxy-spirolactone derivatives: characterization in vivo and in vitro. J Pharmacol Exp Ther 1987, 240:650–656.
Coleman IC, Reddy P, Song CJ, et al.: Eplerenone: the first selective aldosterone receptor antagonist for the treatment of hypertension. Formulary 2002, 37:514–524.
Cook CS, Zhang L, Fischer JS: Absorption and disposition of a selective aldosterone receptor antagonist, eplerenone, in the dog. Pharm Res 2000, 17:1426–1431.
Delyani J, Myles K, Funder J: Eplerenone (SC 66110), a highly selective aldosterone antagonist [abstract]. Am J Hypertens 1998, 11:94A.
Rocha R, Chander PN, Khanna K, et al.: Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats. Hypertension 1998, 31:451–458.
Rocha R, Stier CT Jr, Kifor I, et al.: Aldosterone: a mediator of myocardial necrosis and renal arteriopathy. Endocrinology 2000, 141:3871–3878.
Delyani JA, Robinson EL, Rudolph AE: Effect of a selective aldosterone receptor antagonist in myocardial infarction. Am J Physiol Heart Circ Physiol 2001, 281:H647–654.
Inspra description and product characteristics. Available at: http://www.fda.gov/cder/foi/label/2003/21437sel-002_inspra_lbl.pdf and http://www.nyrdtc.nhsuk/docs/nde/NDE_71_Eplerenone.pdf. Accessed April 12, 2006.
Weinberger MH, Roniker B, Krause SL, Weiss RJ: Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. Am J Hypertens 2002, 15:709–716.
Flack JM, Oparil S, Pratt JH, et al.: Efficacy and tolerability of eplerenone and losartan in hypertensive black and white patients. J Am Coll Cardiol 2003, 41:1148–1155.
Krum H, Nolly H, Workman D, et al.: Efficacy of eplerenone added to renin-angiotensin blockade in hypertensive patients. Hypertension 2002, 40:117–123.
White WB, Duprez D, St Hillaire R, et al.: Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension 2003, 41:1021–1026.
Van Mieghem W, Von Behren V, Balazovjech I, et al.: Eplerenone is safe and effective as an add-on therapy in hypertensive patients uncontrolled with calcium channel blockers or beta blockers [abstract]. Eur Heart J 2002, 23(Suppl):211.
Pitt B, Reichek N, Willenbrock R, et al.: Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation 2003, 108:1831–1838.
Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al.: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003, 348:1309–1321.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Parthasarathy, H.K., MacDonald, T.M. Mineralocorticoid receptor antagonists. Current Science Inc 9, 45–52 (2007). https://doi.org/10.1007/s11906-007-0009-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11906-007-0009-3