Emerging drugs which target the reninangiotensinaldosterone system

Expert Opinion on Emerging Drugs

Volumn 16, Issue 4, 2011, Pages 619-630

  Steckelings, Ulrike Muscha ^a   Paulis, Ludovit ^a,b   Unger, Thomas ^a   Bader, Michael ^c  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b Faculty of Medicine of Comenius University and University Hospital Bratislava   (Slovakia)

^c MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

Author keywords

Aldosterone; Angiotensin; Heart failure; Hypertension

Indexed keywords

ALDOSTERONE ANTAGONIST; ALDOSTERONE SYNTHASE; ALISKIREN; ANGIOTENSIN 1 RECEPTOR ANTAGONIST; ANGIOTENSIN II; ANTIHYPERTENSIVE AGENT; BENAZEPRIL; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BRADYKININ; CANDESARTAN; CAPTOPRIL; CILAZAPRIL; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENALAPRIL; EPLERENONE; FOSINOPRIL; GLITAZONE DERIVATIVE; IRBESARTAN; LISINOPRIL; LOSARTAN; MOEXIPRIL; PERINDOPRIL; QUINAPRIL; RAMIPRIL; RENIN INHIBITOR; SPIRONOLACTONE; STEROID 11BETA MONOOXYGENASE; TELMISARTAN; TRANDOLAPRIL; UNINDEXED DRUG;

ADRENAL GLAND; ANGIONEUROTIC EDEMA; ANTIHYPERTENSIVE ACTIVITY; BLINDNESS; BLOOD PRESSURE; BLOOD VESSEL; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CARDIOVASCULAR SYSTEM; CEREBROVASCULAR DISEASE; CHRONIC DISEASE; CLINICAL TRIAL (TOPIC); CONGESTIVE HEART FAILURE; COUGHING; DIABETES MELLITUS; DIABETIC NEPHROPATHY; DRUG BIOAVAILABILITY; DRUG WITHDRAWAL; EDEMA; EYE DISEASE; GLOMERULOSA CELL; GLUCOSE METABOLISM; GYNECOMASTIA; HALF LIFE TIME; HEART FAILURE; HEART INFARCTION; HEART MUSCLE; HEART MUSCLE FIBROSIS; HUMAN; HYDROCEPHALUS; HYPERALDOSTERONISM; HYPERKALEMIA; HYPERTELORISM; HYPERTENSION; HYPOKALEMIA; IN VITRO STUDY; JUXTAGLOMERULAR APPARATUS; KIDNEY DISEASE; LIBIDO DISORDER; LIFE EXPECTANCY; LIPID METABOLISM; MASTALGIA; MENSTRUAL IRREGULARITY; NERVE REGENERATION; PATIENT COMPLIANCE; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; RETINOPATHY; REVIEW; SIDE EFFECT; STROKE; VASOCONSTRICTION; WATER RETENTION; WEIGHT GAIN;

ALDOSTERONE; ANGIOTENSIN II; ANTIHYPERTENSIVE AGENTS; CLINICAL TRIALS AS TOPIC; DRUG DESIGN; DRUGS, INVESTIGATIONAL; HUMANS; HYPERTENSION; RENIN-ANGIOTENSIN SYSTEM; TREATMENT OUTCOME;

EID: 84555190258     PISSN: 14728214     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728214.2011.618495     Document Type: Review

References (104)

1. Steckelings UM, Unger T. The renin-angiotensin-aldosterone system. Manual of Hypertension of the European Society of Hypertension. Informa Healthcare; London: 2008. p. 110-16
2. Bader M. Tissue renin-angiotensin-aldosterone systems: targets for pharmacological therapy. Annu Rev Pharmacol Toxicol 2010;50:439-65
3. Paul M, Poyan MA, Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev 2006;16:747-803 (Pubitemid 44033382)
4. Nguyen G, Delarue F, Burckle C, et al. Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J Clin Invest 2002;109:1417-27 (Pubitemid 34596167)
5. Burckle C, Bader M. Prorenin and its ancient receptor. Hypertension 2006;48:549-51 (Pubitemid 44843851)
6. Sihn G, Rousselle A, Vil'ianovich L, et al. Physiology of the (pro)renin receptor: wnt of change? Kidney Int 2010;78:246-56
7. Alenina N, Xu P, Rentzsch B, Bader M. Genetically altered animal models for mas and angiotensin-(1-7). Exp Physiol 2008;93:5328-537
8. Steckelings UM, Rompe F, Kaschina E, et al. The past, present and future of angiotensin II type 2 receptor stimulation. J Renin Angiotensin Aldosterone Syst 2010;11:67-73
9. Steckelings UM, Kaschina E, Unger T. The AT2 receptor-a matter of love and hate. Peptides 2005;26:1401-9 (Pubitemid 41021474)
10. Kearney PM, Whelton M, Reynolds K, et al. Global burden of hypertension: analysis of worldwide data. Lancet 2005;365:217-23 (Pubitemid 40138015)
11. Bramlage P, Bohm M, Volpe M, et al. A global perspective on blood pressure treatment and control in a referred cohort of hypertensive patients. J Clin Hypertens (Greenwich) 2010;12:666-77
12. Kotchen TA. Hypertension control: trends, approaches, and goals. Hypertension 2007;49:19-20 (Pubitemid 46360333)
13. Kannel WB. Incidence and epidemiology of heart failure. Heart Fail Rev 2000;5:167-73
14. Redon J. Antihypertensive treatment: should it be titrated to blood pressure reduction or to target organ damage regression? Curr Opin Nephrol Hypertens 2005;14:448-52 (Pubitemid 41152707)
15. Atkins RC. The epidemiology of chronic kidney disease. Kidney Int SUPPL. 2005;94:S14-18
16. Agodoa LY, Jones CA, Held PJ. End-stage renal disease in the USA: data from the United States Renal Data System. Am J Nephrol 1996;16:7-16 (Pubitemid 126506935)
17. Girach A, Manner D, Porta M. Diabetic microvascular complications: can patients at risk be identified? A review. Int J Clin Pract 2006;60:1471-83 (Pubitemid 44560348)
18. Lightman S, Towler HM. Diabetic retinopathy. Clin Cornerstone 2003;5:12-21
19. Buch H, Vinding T, Nielsen NV. Prevalence and causes of visual impairment according to World Health Organization and United States criteria in an aged, urban Scandinavian population: the Copenhagen City Eye Study. Ophthalmology 2001;108:2347-57 (Pubitemid 33096957)
20. Banerjee D, Materson BJ. Blood pressure-independent impact of antihypertensive agents on cardiovascular and renal disease. Curr Hypertens Rep 2002;4:445-52
21. Sleight P. Angiotensin II and trials of cardiovascular outcomes. Am J Cardiol 2002;89:11A-6A
22. European Society of Hypertension-European Society of Cardiology guidelines committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003;21:1011-53
23. Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2007;25:1105-87 (Pubitemid 46924065)
24. Ferreira SH. A bradykinin-potentiating factor (BPF) present in the venom of Bothrops jararaca. Br J Pharmacol 1965;24:163-9
25. Stamler JF, Brody MJ, Phillips MI. The central and peripheral effects of captopril (SQ 14225) on the arterial pressure of the spontaneously hypertensive rat. Brain Res 1980;186:449-503
26. Bangalore S, Kumar S, Messerli FH. Angiotensin-converting enzyme inhibitor associated cough: deceptive information from the Physicians' Desk Reference. Am J Med 2010;123:1016-30
27. Kaplan AP, Greaves MW. Angioedema. J Am Acad Dermatol 2005;53:373-88 (Pubitemid 41195957)
28. Sleight P, Yusuf S, Pogue J, et al. Blood-pressure reduction and cardiovascular risk in HOPE study. Lancet 2001;358:2130-1 (Pubitemid 34094907)
29. Angiotensin-receptor blocker approved as antihypertensive. Am J Health Syst Pharm 1995;52:1368
30. Wong PC, Barnes TB, Chiu AT, et al. Losartan (DuP 753), an orally active nonpeptide angiotensin II receptor antagonist. Cardiovasc Drug Rev 1991;9:317-39
31. Yusuf S, Teo K, Anderson C, et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet 2008;372:1174-83
32. Vidt DG. Telmisartan, ramipril, or both in patients at high risk for vascular events. Curr Hypertens Rep 2008;10:343-4
33. McMurray JJ. Angiotensin inhibition in heart failure. J Renin Angiotensin Aldosterone Syst 2004;5(SUPPL. 1):S17-22 (Pubitemid 39406443)
34. Laverman GD, Remuzzi G, Ruggenenti P. ACE inhibition versus angiotensin receptor blockade: which is better for renal and cardiovascular protection? J Am Soc Nephrol 2004;15(SUPPL. 1):S64-70 (Pubitemid 38018459)
35. Sjolie AK, Dodson P, Hobbs FR. Does renin-angiotensin system blockade have a role in preventing diabetic retinopathy? A clinical review. Int J Clin Pract 2011;65:148-53
36. Lindholm LH, Ibsen H, Dahlof B, et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359:1004-10 (Pubitemid 34286537)
37. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359:995-1003 (Pubitemid 34286536)
38. Bakris G. Are there effects of renin-angiotensin system antagonists beyond blood pressure control? Am J Cardiol 2010;105:21A-9A
39. Bader M, Ganten D. Regulation of renin. J Mol Med 2000;78:130-9
40. Kurtz A. Renin release: sites, mechanisms, and control. Annu Rev Physiol 2011;73:377-99
41. Habashi JP, Doyle JJ, Holm TM, et al. Angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through ERK antagonism. Science 2011;332:361-5
42. Li J, Culman J, Hortnagl H, et al. Angiotensin AT2 receptor protects against cerebral ischemia-induced neuronal injury. FASEB J 2005;19:617-19 (Pubitemid 40471263)
43. Naito T, Ma LJ, Yang H, et al. Angiotensin type 2 receptor actions contribute to angiotensin type 1 receptor blocker effects on kidney fibrosis. Am J Physiol Renal Physiol 2010;298:F683-91
44. Duke LM, Evans RG, Widdop RE. AT2 receptors contribute to acute blood pressure-lowering and vasodilator effects of AT1 receptor antagonism in conscious normotensive but not hypertensive rats. Am J Physiol Heart Circ Physiol 2005;288:H2289-97 (Pubitemid 40604117)
45. Schupp M, Janke J, Clasen R, et al. Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity. Circulation 2004;109:2054-7 (Pubitemid 38620211)
46. Skeggs LT Jr, Kahn JR, Lentz K, Shumway NP. The preparation, purification, and amino acid sequence of a polypeptide renin substrate. J Exp Med 1957;106:439-53
47. Jensen C, Herold P, Brunner HR. Aliskiren: the first renin inhibitor for clinical treatment. Nat Rev Drug Discov 2008;7:399-410 (Pubitemid 351619112)
48. Lee HY, Oh BH. Cardio-renal protection with aliskiren, a direct renin inhibitor, in the ASPIRE HIGHER program. Expert Rev Cardiovasc Ther 2009;7:251-7
49. Rocha R, Funder JW. The pathophysiology of aldosterone in the cardiovascular system. Ann N Y Acad Sci 2002;970:89-100 (Pubitemid 35286086)
50. Funder JW. Aldosterone and mineralocorticoid receptors in the cardiovascular system. Prog Cardiovasc Dis 2010;52:393-400
51. Fitzgerald N, Fitzgerald JD. Aldosterone antagonists: a model of translational medicine. Dialogues Cardiovasc Med 2009;14:118-25
52. Jeunemaitre X, Chatellier G, Kreft-Jais C, et al. Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol 1987;60:820-5 (Pubitemid 17163442)
53. MacFadyen RJ, Lee AF, Morton JJ, et al. How often are angiotensin II and aldosterone concentrations raised during chronic ACE inhibitor treatment in cardiac failure? Heart 1999;82:57-61 (Pubitemid 29309237)
54. 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;341:709-17 (Pubitemid 29407370)
55. Pitt B, White H, Nicolau J, et al. Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. J Am Coll Cardiol 2005;46:425-31 (Pubitemid 41040281)
56. Williams GH, Burgess E, Kolloch RE, et al. Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension. Am J Cardiol 2004;93:990-6 (Pubitemid 38479452)
57. Weinberger MH, White WB, Ruilope LM, et al. Effects of eplerenone versus losartan in patients with low-renin hypertension. Am Heart J 2005;150:426-33 (Pubitemid 41317608)
58. White WB, Duprez D, St HR, et al. Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension 2003;41:1021-6 (Pubitemid 36548598)
59. Krum H, Nolly H, Workman D, et al. Efficacy of eplerenone added to renin-angiotensin blockade in hypertensive patients. Hypertension 2002;40:117-23 (Pubitemid 34840085)
60. Struthers A, Krum H, Williams GH. A comparison of the aldosterone-blocking agents eplerenone and spironolactone. Clin Cardiol 2008;31:153-8 (Pubitemid 351556480)
61. Muldowney JA III, Schoenhard JA, Benge CD. The clinical pharmacology of eplerenone. Expert Opin Drug Metab Toxicol 2009;5:425-32
62. Yamaji M, Tsutamoto T, Kawahara C, et al. Effect of eplerenone versus spironolactone on cortisol and hemoglobin A(c) levels in patients with chronic heart failure. Am Heart J 2010;160:915-21
63. Weinberger MH, Roniker B, Krause SL, Weiss RJ. Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. Am J Hypertens 2002;15:709-16 (Pubitemid 34804277)
64. Violin JD, DeWire SM, Yamashita D, et al. Selectively engaging beta-arrestins at the angiotensin II type 1 receptor reduces blood pressure and increases cardiac performance. J Pharmacol Exp Ther 2010;335:572-9
65. Rakesh K, Yoo B, Kim IM, et al. beta-Arrestin-biased agonism of the angiotensin receptor induced by mechanical stress. Sci Signal 2010;3:ra46
66. Duchene J, Bader M. Bradykinin B2 receptor agonism: A novel therapeutic strategy for myocardial infarction? Am J Hypertens 2010;23:459
67. Kuwahara K, Nakao K. Regulation and significance of atrial and brain natriuretic peptides as cardiac hormones. Endocr J 2010;57:555-65
68. Campbell DJ. Vasopeptidase inhibition: a double-edged sword? Hypertension 2003;41:383-9 (Pubitemid 36314604)
69. Gros C, Noel N, Souque A, et al. Mixed inhibitors of angiotensin- converting enzyme (EC 3.4.15.1) and enkephalinase (EC 3.4.24. 11): rational design, properties, and potential cardiovascular applications of glycopril and alatriopril. Proc Natl Acad Sci USA 1991;88:4210-14 (Pubitemid 21914509)
70. Jullien N, Makritis A, Georgiadis D, et al. Phosphinic tripeptides as dual angiotensin-converting enzyme C-domain and endothelin-converting enzyme-1 inhibitors. J Med Chem 2010;53:208-20
71. Thorin E, Clozel M. The cardiovascular physiology and pharmacology of endothelin-1. Adv Pharmacol 2010;60:1-26
72. Akif M, Schwager SL, Anthony CS, et al. Novel mechanism of inhibition of human angiotensin-I-converting enzyme (ACE) by a highly specific phosphinic tripeptide. Biochem J 2011;436:53-9
73. Gu J, Noe A, Chandra P, et al. Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi). J Clin Pharmacol 2010;50:401-14
74. Lucchese B. Hypertension: LCZ696, a novel dual inhibitor of neprilysin and the angiotensin II receptor, shows promise in phase II trial. Nat Rev Nephrol 2010;6:383
75. Iwata N, Tsubuki S, Takaki Y, et al. Metabolic regulation of brain Abeta by neprilysin. Science 2001;292:1550-2 (Pubitemid 32493424)
76. Becker M, Siems WE, Kluge R, et al. New function for an old enzyme: NEP deficient mice develop late-onset obesity. PLoS One 2010;5(9):e12793. doi:10.1371/journal. pone.0012793
77. Martelli A, Breschi MC, Calderone V. Pharmacodynamic hybrids coupling established cardiovascular mechanisms of action with additional nitric oxide releasing properties. Curr Pharm Des 2009;15:614-36
78. Nguyen G. Renin, (pro)renin and receptor: an update. Clin Sci (Lond) 2011;120:169-78
79. Schefe JH, Menk M, Reinemund J, et al. A novel signal transduction cascade involving direct physical interaction of the renin/prorenin receptor with the transcription factor promyelocytic zinc finger protein. Circ Res 2006;99:1355-66 (Pubitemid 44949671)
80. Inagami T, Nakagawa T, Ichihara A, et al. Renin/prorenin receptor, (P)RR, in end-organ damage: current issues in 2007. J Am Soc Hypertens 2008;2:205-9
81. Ichihara A, Hayashi M, Kaneshiro Y, et al. Inhibition of diabetic nephropathy by a decoy peptide corresponding to the "handle" region for nonproteolytic activation of prorenin. J Clin Invest 2004;114:1128-35 (Pubitemid 39578702)
82. Funke-Kaiser H, Zollmann FS, Schefe JH, Unger T. Signal transduction of the (pro)renin receptor as a novel therapeutic target for preventing end-organ damage. Hypertens Res 2010;33:98-104
83. Nariai T, Fujita K, Mori M, et al. SM-368229, a novel selective and potent non-steroidal mineralocorticoid receptor antagonist with strong urinary Na(+) excretion activity. J Pharmacol Sci 2011;115:346-53
84. Paulis L, Unger T. Novel therapeutic targets for hypertension. Nat Rev Cardiol 2010;7:431-41
85. Fiebeler A, Nussberger J, Shagdarsuren E, et al. Aldosterone synthase inhibitor ameliorates angiotensin II-induced organ damage. Circulation 2005;111:3087-94 (Pubitemid 40847786)
86. Lea WB, Kwak ES, Luther JM, et al. Aldosterone antagonism or synthase inhibition reduces end-organ damage induced by treatment with angiotensin and high salt. Kidney Int 2009;75:936-44
87. Mulder P, Mellin V, Favre J, et al. Aldosterone synthase inhibition improves cardiovascular function and structure in rats with heart failure: a comparison with spironolactone. Eur Heart J 2008;29:2171-9
88. Amar L, Azizi M, Menard J, et al. Aldosterone synthase inhibition with LCI699: a proof-of-concept study in patients with primary aldosteronism. Hypertension 2010;56:831-8
89. Funder JW. Mineralocorticoid receptors: distribution and activation. Heart Fail Rev 2005;10:15-22 (Pubitemid 40895312)
90. Brown MJ. Success and failure of vaccines against renin-angiotensin system components. Nat Rev Cardiol 2009;6:639-47
91. Tissot AC, Maurer P, Nussberger J, et al. Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study. Lancet 2008;371:821-7 (Pubitemid 351323893)
92. Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 2005;11:875-9 (Pubitemid 41161120)
93. Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 2005;436:112-16 (Pubitemid 40966195)
94. Ferreira AJ, Shenoy V, Qi Y, et al. Angiotensin-converting enzyme 2 activation protects against hypertension-induced cardiac fibrosis involving extracellular signal-regulated kinases. Exp Physiol 2011;96:287-94
95. Lula I, Denadai AL, Resende JM, et al. Study of angiotensin-(1-7) vasoactive peptide and its beta-cyclodextrin inclusion complexes: complete sequence-specific NMR assignments and structural studies. Peptides 2007;28:2199-210 (Pubitemid 47610792)
96. Fraga-Silva RA, Costa-Fraga FP, Sousa FB, et al. An orally-active formulation of angiotensin-(1-7) produces antithrombotic effect. Clinics 2011;In press
97. Savergnini SQ, Beiman M, Lautner RQ, et al. Vascular relaxation, antihypertensive effect, and cardioprotection of a novel peptide agonist of the Mas receptor. Hypertension 2010;56:112-20
98. Marques FD, Ferreira AJ, Sinisterra RD, et al. An oral formulation of angiotensin-(1-7) produces cardioprotective effects in infarcted and isoproterenol-treated rats. Hypertension 2011;57:477-83
99. Wiemer G, Dobrucki LW, Louka FR, et al. AVE 0991, a nonpeptide mimic of the effects of angiotensin-(1-7) on the endothelium. Hypertension 2002;40:847-52 (Pubitemid 35434905)
100. Wan Y, Wallinder C, Plouffe B, et al. Design, synthesis, and biological evaluation of the first selective nonpeptide AT2 receptor agonist. J Med Chem 2004;47:5995-6008 (Pubitemid 39507341)
101. Steckelings UM, Larhed M, Hallberg A, et al. Non-peptide AT2-receptor agonists. Curr Opin Pharmacol 2011;11:187-92
102. Esler MD, Krum H, Sobotka PA, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet 2010;376:1903-9
103. Radonic T, De Witte P, Baars MJ, et al. COMPARE study group: Losartan therapy in adults with Marfan syndrome: study protocol of the multi-center randomized controlled COMPARE trial. Trials 2010;12:11-3104
104. Habashi JP, Doyle JJ, Holm TM, et al. Angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through ERK antagonism. Science 2011;332:361-5