Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
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Overview of the Renin-Angiotensin System

  • Ryu, Wang-Seong (Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Kim, Sang-Wook (Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Kim, Chee-Jeong (Department of Internal Medicine, College of Medicine, Chung-Ang University)
  • Published : 2007.03.30
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Abstract

Angiotensin II is an octapeptide hormone of the renin-angiotensin system (RAS), and it regulates a wide variety of physiological responses including salt and water balance, the blood pressure and the vascular tone. Clinical trials with angiotensin-converting enzyme (ACE) inhibitors have demonstrated survival benefits in subjects with congestive heart failure and myocardial infarction, and this support the importance of angiotensin II in the pathogenesis of cardiovascular diseases. Through activation of small G proteins such as Ras, Rho, and Rac, angiotensin II induces remodeling of vascular smooth muscle cells (VSMC), including proliferation, migration, hypertrophy and inflammation. Angiotensin (1-7) appears to be the main effector peptide of ACE2 with vasodilatory, natriuretic and antiinflammatory properties. The cross-talk between the angiotensin II receptors may play an important role in maintaining cardiovascular homeostasis. (Korean Circulation J 2007;37:91-96)

Keywords

References

  1. Duprez DA. Role of the renin-angiotensin-aldosterone system in vascular remodeling and inflammation: a clinical review. J Hypertens 2006;24:983-91
  2. Ohtsu H, Suzuki H, Nakashima H, et al. Angiotensin II signal transduction through small GTP-binding proteins: mechanism and significance in vascular smooth muscle cells. Hypertension 2006; 48:534-40 https://doi.org/10.1161/01.HYP.0000237975.90870.eb
  3. Kim KB. The role of angiotensin receptor antagonist in patients with hypertension and cardiovascular diseases. Korean Circ J 1999;29:335-40 https://doi.org/10.4070/kcj.1999.29.3.335
  4. Dzau V. The cardiovascular continuum and renin-angiotensinaldosterone system blockade. J Hypertens Suppl 2005;23:S9-17 https://doi.org/10.1097/01.hjh.0000165623.72310.dd
  5. Burnier M, Zanchi A. Blockade of the renin-angiotensin-aldosterone system: a key therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes. J Hypertens 2006; 24:11-25 https://doi.org/10.1097/01.hjh.0000191244.91314.9d
  6. Weber MA. Hypertension treatment and implications of recent cardiovascular outcome trials. J Hypertens Suppl 2006;24:S37-44 https://doi.org/10.1097/01.hjh.0000220102.35025.eb
  7. Sokol SI, Portnay EL, Curtis JP, et al. Modulation of the reninangiotensin- aldosterone system for the secondary prevention of stroke. Neurology 2004;63:208-13 https://doi.org/10.1212/01.WNL.0000130360.21618.D0
  8. Sleight P, Yusuf S. New evidence on the importance of the reninangiotensin system in the treatment of higher-risk patients with hypertension. J Hypertens 2003;21:1599-608 https://doi.org/10.1097/00004872-200309000-00001
  9. Jeon ES. Role of angiotensin II receptor blockers in the treatment of congestive heart failure. Korean Circ J 2002;32:1039-45 https://doi.org/10.4070/kcj.2002.32.12.1039
  10. Mancia G. Total cardiovascular risk: a new treatment concept. J Hypertens Suppl 2006;24:S17-24 https://doi.org/10.1097/01.hjh.0000220099.12154.c1
  11. Danilczyk U, Penninger JM. Angiotensin-converting enzyme II in the heart and the kidney. Circ Res 2006;98:463-71 https://doi.org/10.1161/01.RES.0000205761.22353.5f
  12. Farmer JA. Renin angiotensin system and ASCVD. Curr Opin Cardiol 2000;15:141-50 https://doi.org/10.1097/00001573-200005000-00004
  13. Ulfendahl HR, Aurell M. Renin-Angiotensin: a centenary symposium of the discovery of the renin-angiotensin system. London: Portland Press; 1998. p.1-12
  14. Suh SY, Park CG, Chwe UR, et al. Plasma renin activity and clinical implication in Korean hypertensive patients. Korean Circ J 2005;35:658-64 https://doi.org/10.4070/kcj.2005.35.9.658
  15. Duff JL, Marrero MB, Paxton WG, Schieffer B, Bernstein KE, Berk BC. Angiotensin II signal transduction and the mitogenactivated protein kinase pathway. Cardiovasc Res 1995;30:511-7 https://doi.org/10.1016/S0008-6363(95)00088-7
  16. Pan L, Gross KW. Transcriptional regulation of renin. Hypertension 2005;45:3-8 https://doi.org/10.1161/01.HYP.0000151886.26341.4b
  17. Rosendorff C. The renin-angiotensin system and vascular hypertrophy. J Am Coll Cardiol 1996;28:803-12 https://doi.org/10.1016/S0735-1097(96)00251-3
  18. Beierwaltes WH. Renin synthesis and secretion. In: Izzo JL, Black HR, editor. Hypertension Primer. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2003. p.14-7
  19. Krum H, Gilbert RE. Novel therapies blocking the renin-angiotensin- aldosterone system in the management of hypertension and related disorders. J Hypertens 2007;25:25-35 https://doi.org/10.1097/HJH.0b013e3280113950
  20. Berk BC, Corson MA. Angiotensin II signal transduction in vascular smooth muscle: role of tyrosine kinases. Circ Res 1997;80: 607-16 https://doi.org/10.1161/01.RES.80.5.607
  21. de Leeuw PW. How do angiotensin II receptor antagonists affect blood pressure? Am J Cardiol 1999;84:5K-6K https://doi.org/10.1016/S0002-9149(99)00399-9
  22. Min LJ, Mogi M, Li JM, Iwanami J, Iwai M, Horiuchi M. Aldosterone and angiotensin II synergistically induce mitogenic response in vascular smooth muscle cells. Circ Res 2005;97: 434-42 https://doi.org/10.1161/01.RES.0000180753.63183.95
  23. Zhang Y, Griendling KK, Dikalova A, Owens GK, Taylor WR. Vascular hypertrophy in angiotensin II-induced hypertension is mediated by vascular smooth muscle cell-derived $H_2O_2$. Hypertension 2005;46:732-7 https://doi.org/10.1161/01.HYP.0000182660.74266.6d
  24. Ushio-Fukai M, Zuo L, Ikeda S, Tojo T, Patrushev NA, Alexander RW. cAbl tyrosine kinase mediates reactive oxygen species and caveolin-dependent $AT_1$ receptor signaling in vascular smooth muscle. Circ Res 2005;97:829-36 https://doi.org/10.1161/01.RES.0000185322.46009.F5
  25. Dikalova A, Clempus R, Lassegue B, et al. Nox1 overexpression potentiates angiotensin II-induced hypertension and vascular smooth muscle hypertrophy in transgenic mice. Circulation 2005; 112:2668-76 https://doi.org/10.1161/CIRCULATIONAHA.105.538934
  26. Shimokawa H. Rho-kinase as a novel therapeutic target in treatment of cardiovascular diseases. J Cardiovasc Phamacol 2002; 39:319-27 https://doi.org/10.1097/00005344-200203000-00001
  27. Calo LA, Pessina AC. RhoA/Rho-kinase pathway: much more than just a modulation of vascular tone: evidence from studies in humans. J Hypertens 2007;25:259-64 https://doi.org/10.1097/HJH.0b013e328010d4d2
  28. Smith NJ, Luttrell LM. Signal switching, crosstalk, and arrestin scaffolds: novel G protein-coupled receptor signaling in cardiovascular disease. Hypertension 2006;48:173-9 https://doi.org/10.1161/01.HYP.0000232641.84521.92
  29. Yang CH, Lee SH, Park TH, et al. Gene expression profile of volume-overloaded human ventricular myocardium prior to developing heart failure. Korean Circ J 2005;35:649-57 https://doi.org/10.4070/kcj.2005.35.9.649
  30. Fleming I. Signaling by the angiotensin-converting enzyme. Circ Res 2006;98:887-96 https://doi.org/10.1161/01.RES.0000217340.40936.53
  31. Willenheimer R, Dahloef B, Rydberg E, Erhardt L. AT1-receptor blockers in hypertension and heart failure: clinical experience and future directions. Eur Heart J 1999;20:997-1008 https://doi.org/10.1053/euhj.1999.1547
  32. Hollenberg NK. Hypertension, small arteries, and pathways for angiotensin II generation. Circulation 2000;101:1641-2 https://doi.org/10.1161/01.CIR.101.14.1641
  33. Unger T, Culman J, Peter G. Angiotensin II receptor blockade and end-organ protection: pharmacological rationale and evidence. J Hypertens Suppl 1998;16:S3-9 https://doi.org/10.1097/00004872-199816010-00002
  34. Diez J. Profibrotic effects of angiotensin II in the heart. Hypertension 2004;43:1164-5 https://doi.org/10.1161/01.HYP.0000128620.57061.67
  35. Wolf G, Wenzel UO. Angiotensin II and cell cycle regulation. Hypertension 2004;43:693-8 https://doi.org/10.1161/01.HYP.0000120963.09029.ca
  36. Kim YH, Son JH, Piao H, et al. Role of angiotensin II type 1A receptor-mediated signaling in the development of pressure overload- induced left ventricular hypertrophy and fibrosis. Korean Circ J 2006;36:626-34 https://doi.org/10.4070/kcj.2006.36.9.626
  37. Kim KM, Kim IS, Park SJ, et al. Effects of angiotensin II on the growth of vascular smooth muscle cells. Korean Circ J 1999;29: 209-15 https://doi.org/10.4070/kcj.1999.29.2.209
  38. Dielis AW, Smid M, Spronk HM, et al. The prothrombotic paradox of hypertension: role of the renin-angiotensin and kallikreinkinin systems. Hypertension 2005;46:1236-42 https://doi.org/10.1161/01.HYP.0000193538.20705.23
  39. Sampaio WO, Souza dos Santos RA, Faria-Silva R, de Mata Machado LT, Schiffrin EL, Touyz RM. Angiotensin-(1-7) through receptor Mas mediates endothelial nitric oxide synthase activation via Akt-dependent pathways. Hypertension 2007;49:185-92 https://doi.org/10.1161/01.HYP.0000251865.35728.2f
  40. Brown NJ, Vaughan DE. Angiotensin-converting enzyme inhibitors. Circulation 1998;97:1411-20 https://doi.org/10.1161/01.CIR.97.14.1411
  41. Sayed-Tabatabaei FA, Oostra BA, Isaacs A, van Duijn CM, Witteman JC. ACE polymorphisms. Circ Res 2006;98:1123-33 https://doi.org/10.1161/01.RES.0000223145.74217.e7
  42. Goldberg LR, Jessup M. Stage B heart failure: management of asymptomatic left ventricular systolic dysfunction. Circulation 2006;113:2851-60 https://doi.org/10.1161/CIRCULATIONAHA.105.600437
  43. Kahan T. The importance of left ventricular hypertrophy in human hypertension. J Hypertens Suppl 1998;16:S23-9 https://doi.org/10.1097/00004872-199816010-00005
  44. Alfakin K, Reid S, Hall A, Sivananthan MU. The assessment of left ventricular hypertrophy in hypertension. J Hypertens 2006; 24:1223-30 https://doi.org/10.1097/01.hjh.0000234097.47379.fd
  45. Gosse P. Left ventricular hypertrophy as a predictor of cardiovascular risk. J Hypertens Suppl 2005;23:S27-33 https://doi.org/10.1097/01.hjh.0000165625.79933.9a
  46. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86:1343-6 https://doi.org/10.1172/JCI114844
  47. Rigat B, Hubert C, Corvol P, Soubrier F. PCR detection of the insertion/deletion polymorphism of the human angiotensin-converting enzyme gene (DCPI) (dipeptidyl carboxypeptidase I). Nucleic Acids Res 1992;20:1433
  48. Rosendorff C. Vascular hypertrophy in hypertension: role of the renin-angiotensin system. Mt Sinai J Med 1998;65:108-17
  49. Schiffrin EL. Effects of antihypertensive drugs on vascular remodeling: do they predict outcome in response to antihypertensive therapy? Curr Opin Nephrol Hypertens 2001;10:617-24 https://doi.org/10.1097/00041552-200109000-00011
  50. Schulman IH, Zhou MS, Raij L. Cross-talk between angiotensin II receptor types 1 and 2: potential role in vascular remodeling in humans. Hypertension 2007;49:270-1 https://doi.org/10.1161/01.HYP.0000253966.21795.d3
  51. Burnier M. Angiotensin II type 1 receptor blockers. Circulation 2001;103:904-12 https://doi.org/10.1161/01.CIR.103.6.904