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Rethinking the Renin-Angiotensin System and Its Role in Cardiovascular Regulation
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  • Review Article
  • Published: January 2005

Rethinking the Renin-Angiotensin System and Its Role in Cardiovascular Regulation

  • Pasquale Pagliaro MD PhD1,2 &
  • Claudia Penna1 

Cardiovascular Drugs and Therapy volume 19, pages 77–87 (2005)Cite this article

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Abstract

Angiotensin-converting enzyme (ACE) plays a pivotal role in the renin-angiotensin system (RAS) and ACE-inhibitors are widely used in several clinical conditions, including hypertension and heart failure. Recently, a homologue of ACE, ACE2 has been discovered. Both ACE and ACE2 are emerging as key enzymes of the RAS, where ACE2 may play a role as negative regulator of ACE. Moreover, ACE2 appears to be an important enzyme outside the classical RAS, as it hydrolyzes apelins, dynorphin A 1-13, des-Arg-bradykinin and other peptide substrates. The precise interplay between tissue ACE, ACE2, and their substrates and by-products are presently still unclear.

ACE-inhibitors reduce angiotensin II formation and bradykinin degradation, but do not inhibit ACE2 activity. Moreover, ACE-inhibitors differ in their affinity for tissue ACE, and it has been suggested that tissue ACE affinity might be responsible for some of the beneficial properties of these drugs. ACE-inhibitors also increase nitric oxide availability, and activate several kinases that may regulate protein synthesis by interacting with the nucleus of the cells (outside-in signaling). The outside-in signaling may also be activated by bradykinin itself. Although, the precise significance of the outside-in signaling is still unclear, this new role of ACE-inhibitors may represent a discriminant factor versus angiotensin II receptors antagonists.

This mini review will summarize some new aspects concerning the recently discovered biological functions of RAS and in particular of ACE, ACE2 and ACE-inhibitors in cardiovascular system.

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References

  1. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 2000;275:33238–33243.

    CAS  PubMed  Google Scholar 

  2. Rastaldo R, Paolocci N, Chiribiri A, Penna C, Gattullo D, Pagliaro P. Cytochrome P-450 metabolite of arachidonic acid mediates bradykinin-induced negative inotropic effect. Am J Physiol Heart Circ Physiol 2001;280:H2823–2832.

    CAS  PubMed  Google Scholar 

  3. Kohlstedt K, Shoghi F, Muller-Esterl W, Busse R, Fleming I. CK2 phosphorylates the angiotensin-converting enzyme and regulates its retention in the endothelial cell plasma membrane. Circ Res 2002;91:749–756.

    CAS  PubMed  Google Scholar 

  4. Kohlstedt K, Busse R, Fleming I. Signaling via the Angiotensin-Converting Enzyme Enhances the Expression of Cyclooxygenase-2 in Endothelial Cells. Hypertension 2005;45:126–132.

    CAS  PubMed  Google Scholar 

  5. Kohlstedt K, Brandes RP, Muller-Esterl W, Busse R, Fleming I. Angiotensin-converting enzyme is involved in outside-in signaling in endothelial cells. Circ Res 2004;94:60– 67.

    CAS  PubMed  Google Scholar 

  6. Ng KK, Vane JR. Fate of angiotensin I in the circulation. Nature 1968;218:144–150.

    CAS  PubMed  Google Scholar 

  7. Ng KK, Vane JR. The conversion of angiotensin I to angiotensin II in vivo. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol 1968;259:188–189.

    CAS  PubMed  Google Scholar 

  8. Yamada H, Fabris B, Allen AM, Jackson B, Johnston CI, Mendelsohn AO. Localization of angiotensin converting enzyme in rat heart. Circ Res 1991;68:141–149.

    CAS  PubMed  Google Scholar 

  9. Falkenhahn M, Franke F, Bohle RM, et al. Cellular distribution of angiotensin-converting enzyme after myocardial infarction. Hypertension 1995;25:219–226.

    CAS  PubMed  Google Scholar 

  10. Hirsch AT, Talsness CE, Schunkert H, Paul M, Dzau VJ. Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure. Circ Res 1991;69:475–482.

    CAS  PubMed  Google Scholar 

  11. Schunkert H, Ingelfinger JR, Hirsch AT, et al. Evidence for tissue-specific activation of renal angiotensinogen mRNA expression in chronic stable experimental heart failure. J Clin Invest 1992;90:1523–1529.

    CAS  PubMed  Google Scholar 

  12. Leri A, Claudio PP, Li Q, et al. Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell. J Clin Invest 1998;101:1326–1342.

    CAS  PubMed  Google Scholar 

  13. Rajagopalan S, Kurz S, Munzel T, et al. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 1996;97:1916–1923.

    CAS  PubMed  Google Scholar 

  14. Gattullo D, Pagliaro P, Marsh NA, Losano G. New insights into nitric oxide and coronary circulation. Life Sci 1999;65:2167–2174.

    CAS  PubMed  Google Scholar 

  15. Hokimoto S, Yasue H, Fujimoto K, et al. Expression of angiotensin-converting enzyme in remaining viable myocytes of human ventricles after myocardial infarction. Circulation 1996;94:1513–1518.

    CAS  PubMed  Google Scholar 

  16. de Lannoy LM, Danser AH, Bouhuizen AM, Saxena PR, Schalekamp MA. Localization and production of angiotensin II in the isolated perfused rat heart. Hypertension 1998;31:1111–1117.

    CAS  PubMed  Google Scholar 

  17. Urata H, Kinoshita A, Misono KS, Bumpus FM, Husain A. Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart. J Biol Chem 1990;265:22348–22357.

    CAS  PubMed  Google Scholar 

  18. Ruzicka M, Skarda V, Leenen FH. Effects of ACE inhibitors on circulating versus cardiac angiotensin II in volume overload-induced cardiac hypertrophy in rats. Circulation 1995;92:3568–3573.

    CAS  PubMed  Google Scholar 

  19. Lee YA, Liang CS, Lee MA, Lindpaintner K. Local stress, not systemic factors, regulate gene expression of the cardiac renin-angiotensin system in vivo: A comprehensive study of all its components in the dog. Proc Natl Acad Sci USA 1996;93:11035–11040.

    CAS  PubMed  Google Scholar 

  20. Sadoshima J, Xu Y, Slayter HS, Izumo S. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 1993;75:977–984.

    CAS  PubMed  Google Scholar 

  21. Pfeifer M, Bruckschlegel G, Holmer SR, Paul M, Riegger AJ, Schunkert H. Reciprocal regulation of pulmonary and cardiac angiotensin-converting enzyme in rats with severe left ventricular hypertrophy. Cardiovasc Res 1998;38:125–132.

    CAS  PubMed  Google Scholar 

  22. Lowes BD, Minobe W, Abraham WT, et al. Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium. J Clin Invest 1997;100:2315–2324.

    CAS  PubMed  Google Scholar 

  23. Pinto YM, van Gilst WH, Kingma JH, Schunkert H. Deletion-type allele of the angiotensin-converting enzyme gene is associated with progressive ventricular dilation after anterior myocardial infarction. Captopril and Thrombolysis Study Investigators. J Am Coll Cardiol 1995;25:1622–1626.

    CAS  PubMed  Google Scholar 

  24. Ohmichi N, Iwai N, Maeda K, et al. Genetic basis of left ventricular remodeling after myocardial infarction. Int J Cardiol 1996;53:265–272.

    CAS  PubMed  Google Scholar 

  25. Turner ST, Boerwinkle E, Sing CF. Context-dependent associations of the ACE I/D polymorphism with blood pressure. Hypertension 1999;34:773–778.

    CAS  PubMed  Google Scholar 

  26. Pfohl M, Koch M, Prescod S, Haase KK, Haring HU, Karsch KR. Angiotensin I-converting enzyme gene polymorphism, coronary artery disease and myocardial infarction. An angiographically controlled study. Eur Heart J 1999;20:1318–1325.

    CAS  PubMed  Google Scholar 

  27. Davies CH, Davia K, Bennett JG, Pepper JR, Poole-Wilson PA, Harding SE. Reduced contraction and altered frequency response of isolated ventricular myocytes from patients with heart failure. Circulation 1995;92:2540–2549.

    CAS  PubMed  Google Scholar 

  28. Frey N, Olson EN. Cardiac hypertrophy: The good, the bad, and the ugly. Annu Rev Physiol 2003;65:45–79.

    CAS  PubMed  Google Scholar 

  29. Schluter KD, Wollert KC. Synchronization and integration of multiple hypertrophic pathways in the heart. Cardiovasc Res 2004;63:367–372.

    CAS  PubMed  Google Scholar 

  30. Thomas WG, Brandenburger Y, Autelitano DJ, Pham T, Qian H, Hannan RD. Adenoviral-directed expression of the type 1A angiotensin receptor promotes cardiomyocyte hypertrophy via transactivation of the epidermal growth factor receptor. Circ Res 2002;90:135–142.

    CAS  PubMed  Google Scholar 

  31. Rocic P, Govindarajan G, Sabri A, Lucchesi PA. A role for PYK2 in regulation of ERK1/2 MAP kinases and PI 3-kinase by ANG II in vascular smooth muscle. Am J Physiol Cell Physiol 2001;280:C90–C99.

    CAS  PubMed  Google Scholar 

  32. Daub H, Weiss FU, Wallasch C, Ullrich A. Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature 1996;379:557–560.

    CAS  PubMed  Google Scholar 

  33. Seta K, Nanamori M, Modrall JG, Neubig RR, Sadoshima J. AT1 receptor mutant lacking heterotrimeric G protein coupling activates the Src-Ras-ERK pathway without nuclear translocation of ERKs. J Biol Chem 2002;277:9268–9277.

    CAS  PubMed  Google Scholar 

  34. Xia Y, Karmazyn M. Obligatory role for endogenous endothelin in mediating the hypertrophic effects of phenylephrine and angiotensin II in neonatal rat ventricular myocytes: Evidence for two distinct mechanisms for endothelin regulation. J Pharmacol Exp Ther 2004;310:43– 51.

    CAS  PubMed  Google Scholar 

  35. Pellieux C, Foletti A, Peduto G, et al. Dilated cardiomyopathy and impaired cardiac hypertrophic response to angiotensin II in mice lacking FGF-2. J Clin Invest 2001;108:1843–1851.

    CAS  PubMed  Google Scholar 

  36. Packer M. The impossible task of developing a new treatment for heart failure. J Card Fail 2002;8:193–196.

    PubMed  Google Scholar 

  37. Remme WJ. Pharmacological modulation of cardiovascular remodeling: A guide to heart failure therapy. Cardiovasc Drugs Ther 2003;17:349–360.

    CAS  PubMed  Google Scholar 

  38. Flather MD, Yusuf S, Kober L, et al. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: A systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet 2000;355:1575–1581.

    CAS  PubMed  Google Scholar 

  39. Ohta T, Hasebe N, Tsuji S, et al. Unequal effects of renin-angiotensin system inhibitors in acute cardiac dysfunction induced by isoproterenol. Am J Physiol Heart Circ Physiol 2004;287:H2914–H2921.

    CAS  PubMed  Google Scholar 

  40. Fox KM. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: Randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003;362:782–788.

    CAS  PubMed  Google Scholar 

  41. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:145–153.

    Article  PubMed  Google Scholar 

  42. Remme WJ. Should ACE inhibition always be first-line therapy in heart failure? Lessons from the CARMEN Study. Cardiovasc Drugs Ther 2003;17:107–109.

    CAS  PubMed  Google Scholar 

  43. Pfeffer JM, Pfeffer MA, Mirsky I, Braunwald E. Regression of left ventricular hypertrophy and prevention of left ventricular dysfunction by captopril in the spontaneously hypertensive rat. Proc Natl Acad Sci USA 1982;79:3310–3314.

    CAS  PubMed  Google Scholar 

  44. Fleischmann EH, Schmieder RE. Are all antihypertensive drug classes equal in reducing left ventricular hypertrophy? Curr Cardiol Rep 2002;4:474–478.

    PubMed  Google Scholar 

  45. Eichhorn EJ, Bristow MR. Medical therapy can improve the biological properties of the chronically failing heart. A new era in the treatment of heart failure. Circulation 1996;94:2285–2296.

    CAS  PubMed  Google Scholar 

  46. Dzau VJ, Bernstein K, Celermajer D, et al. The relevance of tissue angiotensin-converting enzyme: Manifestations in mechanistic and endpoint data. Am J Cardiol 2001;88:1L–20L.

    CAS  PubMed  Google Scholar 

  47. Dzau VJ, Bernstein K, Celermajer D, et al. Pathophysiologic and therapeutic importance of tissue ACE: A consensus report. Cardiovasc Drugs Ther 2002;16:149–160.

    CAS  PubMed  Google Scholar 

  48. Sauer WH, Baer JT, Berlin JA, Kimmel SE. Class effect of angiotensin-converting enzyme inhibitors on prevention of myocardial infarction. Am J Cardiol 2004;94:1171–1173.

    CAS  PubMed  Google Scholar 

  49. Fabris B, Chen BZ, Pupic V, Perich R, Johnston CI. Inhibition of angiotensin-converting enzyme (ACE) in plasma and tissue. J Cardiovasc Pharmacol 1990;15(Suppl 2):S6– S13.

    CAS  Google Scholar 

  50. Kinoshita A, Urata H, Bumpus FM, Husain A. Measurement of angiotensin I converting enzyme inhibition in the heart. Circ Res 1993;73:51–60.

    CAS  PubMed  Google Scholar 

  51. Yagil C, Sapojnikov M, Kreutz R, Zurcher H, Ganten D, Yagil Y. Role of chromosome X in the Sabra rat model of salt-sensitive hypertension. Hypertension 1999;33:261–265.

    CAS  PubMed  Google Scholar 

  52. Crackower MA, Sarao R, Oudit GY, et al. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 2002;417:822–828.

    CAS  PubMed  Google Scholar 

  53. Donoghue M, Hsieh F, Baronas E, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res 2000;87:E1–E9.

    CAS  PubMed  Google Scholar 

  54. Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett 2002;532:107–110.

    CAS  PubMed  Google Scholar 

  55. Komatsu T, Suzuki Y, Imai J, et al. Molecular cloning, mRNA expression and chromosomal localization of mouse angiotensin-converting enzyme-related carboxypeptidase (mACE2). DNA Seq 2002;13:217–220.

    CAS  PubMed  Google Scholar 

  56. Warner FJ, Smith AI, Hooper NM, Turner AJ. Angiotensin-converting enzyme-2: A molecular and cellular perspective. Cell Mol Life Sci 2004;61:2704–2713.

    CAS  PubMed  Google Scholar 

  57. Chen AA, Barnes G, Foti A, Nolin E, Lewitzsky S, Metivier J. Two single nucleotide polymorphisms in theACE2 locus are associated with cardiovascular disease. Gen Epidem 2002;23:272(Abs).

    Google Scholar 

  58. Iyer SN, Averill DB, Chappell MC, Yamada K, Allred AJ, Ferrario CM. Contribution of angiotensin-(1-7) to blood pressure regulation in salt-depleted hypertensive rats. Hypertension 2000;36:417–422.

    CAS  PubMed  Google Scholar 

  59. Ren Y, Garvin JL, Carretero OA. Vasodilator action of angiotensin-(1-7) on isolated rabbit afferent arterioles. Hypertension 2002;39:799–802.

    CAS  PubMed  Google Scholar 

  60. Huang L, Sexton DJ, Skogerson K, et al. Novel peptide inhibitors of angiotensin-converting enzyme 2. J Biol Chem 2003;278:15532–15540.

    CAS  PubMed  Google Scholar 

  61. Turner AJ, Hooper NM. The angiotensin-converting enzyme gene family: Genomics and pharmacology. Trends Pharmacol Sci 2002;23:177–183.

    CAS  PubMed  Google Scholar 

  62. Krege JH, John SW, Langenbach LL, et al. Male-female differences in fertility and blood pressure in ACE-deficient mice. Nature 1995;375:146–148.

    CAS  PubMed  Google Scholar 

  63. Oudit GY, Crackower MA, Backx PH, Penninger JM. The role of ACE2 in cardiovascular physiology. Trends Cardiovasc Med 2003;13:93–101.

    CAS  PubMed  Google Scholar 

  64. Allred AJ, Donoghue M, Acton S, Coffman TM. Regulation of blood pressure by the angiotensin converting en-zyme homologue ACE2. Am J Nephrol 2002;13:52A(Abs).

    Google Scholar 

  65. Yagil Y, Yagil C. Hypothesis: ACE2 modulates blood pressure in the mammalian organism. Hypertension 2003;41:871–873.

    CAS  PubMed  Google Scholar 

  66. Murphy AM, Kogler H, Georgakopoulos D, et al. Transgenic mouse model of stunned myocardium. Science 2000;287:488–491.

    CAS  PubMed  Google Scholar 

  67. Guy JL, Jackson RM, Acharya KR, Sturrock ED, Hooper NM, Turner AJ. Angiotensin-converting enzyme-2 (ACE2): Comparative modeling of the active site, specificity requirements, and chloride dependence. Biochemistry 2003;42:13185–13192.

    CAS  PubMed  Google Scholar 

  68. Vickers C, Hales P, Kaushik V, et al. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem 2002;277:14838–14843.

    CAS  PubMed  Google Scholar 

  69. Bedendi I, Alloatti G, Marcantoni A, et al. Cardiac effects of ghrelin and its endogenous derivatives des-octanoyl ghrelin and des-Gln14-ghrelin. Eur J Pharmacol 2003;476:87–95.

    CAS  PubMed  Google Scholar 

  70. Tatemoto K, Takayama K, Zou MX, et al. The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism. Regul Pept 2001;99:87–92.

    CAS  PubMed  Google Scholar 

  71. De Mota N, Reaux-Le Goazigo A, El Messari S, et al. Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release. Proc Natl Acad Sci USA 2004;101:10464–10469.

    CAS  PubMed  Google Scholar 

  72. Szokodi I, Tavi P, Foldes G, et al. Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility. Circ Res 2002;91:434–440.

    CAS  PubMed  Google Scholar 

  73. Berry MF, Pirolli TJ, Jayasankar V, et al. Apelin has in vivo inotropic effects on normal and failing hearts. Circulation 2004;110 (11 Suppl 1):II187–II193.

    PubMed  Google Scholar 

  74. Hosoya M, Kawamata Y, Fukusumi S, et al. Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin. J Biol Chem 2000;275:21061–21067.

    CAS  PubMed  Google Scholar 

  75. Ishida J, Hashimoto T, Hashimoto Y, et al. Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo. J Biol Chem 2004;279:26274–26279.

    CAS  PubMed  Google Scholar 

  76. Ashley EA, Powers J, Chen M, et al. The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo. Cardiovasc Res 2005;65:73–82.

    CAS  PubMed  Google Scholar 

  77. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004;203:631– 637.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino, Italy

    Pasquale Pagliaro MD PhD & Claudia Penna

  2. Dipartimento di Scienze Cliniche e, Biologiche, Università di Torino Ospedale S. Luigi, Regione Gonzole, 10043 Orbassano (TO), Italy

    Pasquale Pagliaro MD PhD

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  1. Pasquale Pagliaro MD PhD
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  2. Claudia Penna
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Correspondence to Pasquale Pagliaro MD PhD.

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Pagliaro, P., Penna, C. Rethinking the Renin-Angiotensin System and Its Role in Cardiovascular Regulation. Cardiovasc Drugs Ther 19, 77–87 (2005). https://doi.org/10.1007/s10557-005-6900-8

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  • Issue Date: January 2005

  • DOI: https://doi.org/10.1007/s10557-005-6900-8

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Key Words

  • angiotensin-converting enzyme (ACE)
  • ACE-associated kinases
  • ACE-inhibitors
  • Bradykinin
  • renin-angiotensin system
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