Skip to main content
SpringerLink
Log in

Prehypertension and the Renin-Angiotensin-Aldosterone System

  • Chapter
  • First Online:
Prehypertension and Cardiometabolic Syndrome

Part of the book series: Updates in Hypertension and Cardiovascular Protection ((UHCP))

Abstract

The renin-angiotensin-aldosterone system (RAAS) represents one of the most important contributors to vascular, cardiac, and renal pathology. Its major effector peptides, notably the octapeptide angiotensin II (AngII), induce vasoconstriction (directly and indirectly via sympathetic activation and vasopressin release) and participate in processes of vascular and cardiac hypertrophy, remodeling, inflammation, and fibrosis, directly through action on the angiotensin AT1 receptor and indirectly through aldosterone stimulation. In addition, the RAAS engenders renal salt retention and is involved in various renal pathologies. By the above mechanisms, the RAAS contributes to the development and maintenance of arterial hypertension. RAAS-induced vascular, cardiac, and renal pathologies occur already in the prehypertensive state, i.e., before overt hypertension has developed. Recently, a so-called protective arm of the renin-angiotensin system (RAS) has been described including angiotensin-converting enzyme 2 (ACE2), the angiotensin AT2 receptor, and the Ang 1–7/Mas receptor system. The “protective RAS” appears to represent an intrinsic opponent of the classical “harmful RAS,” and stimulation of this system may become an important therapeutic approach in individuals at cardiovascular risk.

Inhibitors of the “harmful” RAAS (ACE inhibitors, AT1 receptor, and aldosterone receptor antagonists) have been successfully introduced into the clinic with a broad spectrum of indications, particularly as antihypertensive agents. The TROPHY study with the AT1 receptor blocker, candesartan, and in the PHARAO study with the ACE inhibitor, ramipril, have provided evidence that the natural course from prehypertension to hypertension can be delayed, supporting the idea that in certain patient populations at risk, chronic antihypertensive treatment with an inhibitor of the RAS started already in the prehypertensive phase may exert protection by preventing the onset of high blood pressure disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Unger T. The angiotensin type 2 receptor: variations on an enigmatic theme. J Hypertens. 1999;17(12 Pt 2):1775–86.

    Article  CAS  PubMed  Google Scholar 

  2. Kaschina E, Unger T. Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press. 2003;12:70–88.

    Article  CAS  PubMed  Google Scholar 

  3. Namsolleck P, Recarti C, Foulquier S, Steckelings UM, Unger T. AT(2) receptor and tissue injury: therapeutic implications. Curr Hypertens Rep. 2014;16:416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Leonhardt J, Villela DC, Teichmann A, Münter LM, Mayer MC, Mardahl M, et al. Evidence for heterodimerization and functional interaction of the angiotensin type 2 receptor and the receptor MAS. Hypertension. 2017;69(6):1128–35.

    Article  CAS  PubMed  Google Scholar 

  5. Peralta CA, Adeney KL, Shlipak MG, Jacobs D Jr, Duprez D, Bluemke D, et al. Structural and functional vascular alterations and incident hypertension in normotensive adults: the Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol. 2010;171:63–71.

    Article  PubMed  Google Scholar 

  6. Paul M, Poyan Mehr A, Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev. 2006;86(3):747–803.

    Article  CAS  PubMed  Google Scholar 

  7. Harrap SB, Van der Merwe WM, Griffin SA, Macpherson F, Lever AF. Brief angiotensin converting enzyme inhibitor treatment in young spontaneously hypertensive rats reduces blood pressure long-term. Hypertension. 1990;16:603–14.

    Article  CAS  PubMed  Google Scholar 

  8. Lundie MJ, Friberg P, Kline RL, Adams MA. Long-term inhibition of the renin-angiotensin system in genetic hypertension: analysis of the impact on blood pressure and cardiovascular structural changes. J Hypertens. 1997;15:339–48.

    Article  CAS  PubMed  Google Scholar 

  9. Lee RM, Berecek KH, Tsoporis J, McKenzie R, Triggle CR. Prevention of hypertension and vascular changes by captopril treatment. Hypertension. 1991;17:141–50.

    Article  CAS  PubMed  Google Scholar 

  10. Unger T, Mattfeldt T, Lamberty V, Bock P, Mall G, Linz W, Schölkens BA, Gohlke P. Effect of early onset angiotensin converting enzyme inhibition on myocardial capillaries. Hypertension. 1992;20:478–82.

    Article  CAS  PubMed  Google Scholar 

  11. Wu JN, Berecek KH. Prevention of genetic hypertension by early treatment of spontaneously hypertensive rats with the angiotensin converting enzyme inhibitor captopril. Hypertension. 1993;22:139–46.

    Article  CAS  PubMed  Google Scholar 

  12. Unger T, Rettig R. Development of genetic hypertension. Is there a “critical phase”? Hypertension. 1990;16(6):615.

    Article  CAS  PubMed  Google Scholar 

  13. Schiffrin EL, Deng LY, Larochelle P. Effects of a beta-blocker or a converting enzyme inhibitor on resistance arteries in essential hypertension. Hypertension. 1994;23:83–91.

    Article  CAS  PubMed  Google Scholar 

  14. Julius S, Nesbitt SD, Egan BM, Weber MA, Michelson EL, Kaciroti N, et al. Trial of Preventing Hypertension (TROPHY) Study Investigators. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med. 2006;20(354):1685–97.

    Article  Google Scholar 

  15. Lüders S, Schrader J, Berger J, Unger T, Zidek W, Böhm M, et al. The PHARAO study: prevention of hypertension with the angiotensin-converting enzyme inhibitor ramipril in patients with high-normal blood pressure: a prospective, randomized, controlled prevention trial of the German Hypertension League. J Hypertens. 2008;26:1487–96.

    Article  CAS  PubMed  Google Scholar 

  16. Balt JC, Mathy MJ, Pfaffendorf M, van Zwieten PA. Sympatho-inhibitory properties of various AT1 receptor antagonists. J Hypertens Suppl. 2002;20:S3–11.

    Article  CAS  PubMed  Google Scholar 

  17. Hahn AW, Regenass S, Kern F, Bühler FR, Resink TJ. Expression of soluble and insoluble fibronectin in rat aorta: effects of angiotensin II and endothelin-1. Biochem Biophys Res Commun. 1993;192:189–97.

    Article  CAS  PubMed  Google Scholar 

  18. Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res. 1994;74:1141–8.

    Article  CAS  PubMed  Google Scholar 

  19. Zafari AM, Ushio-Fukai M, Akers M, Yin Q, Shah A, Harrison DG, Taylor WR, Griendling KK. Novel role of NADH/NADPH oxidase-derived hydrogen peroxide in angiotensin 11-induced hypertrophy of rat smooth muscle cells. Hypertension. 1998;32:488–95.

    Article  CAS  PubMed  Google Scholar 

  20. Montezano AC, Touyz RM. Reactive oxygen species, vascular Noxs, and hypertension: focus on translational and clinical research. Antioxid Redox Signal. 2014;20:164–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Robert Li Y. Free radical biomedicine: principles, clinical correlations, and methodologies: Bentham eBooks; 2012. https://doi.org/10.2174/97816080532231120101.

    Google Scholar 

  22. Lacolley P, Regnault V, Nicoletti A, Li Z, Michel JB. The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles. Cardiovasc Res. 2012;15(95):194–204.

    Article  CAS  Google Scholar 

  23. Culman J, Baulmann J, Blume A, Unger T. The renin-angiotensin system in the brain: an update. J Renin Angiotensin Aldosterone Syst. 2001;2:96–102.

    Article  CAS  PubMed  Google Scholar 

  24. Burrell LM, Phillips PA, Risvanis J, Aldred KL, Hutchins AM, Johnston CI. Attenuation of genetic hypertension after short-term vasopressin V1A receptor antagonism. Hypertension. 1995;26:828–34.

    Article  CAS  PubMed  Google Scholar 

  25. Burrell LM, Risvanis J, Dean RG, Patel SK, Velkoska E, Johnston CI. Age-dependent regulation of renal vasopressin V(1A) and V2 receptors in rats with genetic hypertension: implications for the treatment of hypertension. J Am Soc Hypertens. 2013;7:3–13.

    Article  CAS  PubMed  Google Scholar 

  26. Bussien JP, Waeber B, Nussberger J, Schaller MD, Gavras H, Hofbauer K, et al. Does vasopressin sustain blood pressure of normally hydrated healthy volunteers? Am J Physiol. 1984;246(1 Pt 2):H143–7.

    CAS  PubMed  Google Scholar 

  27. Waeber B, Nussberger J, Hofbauer KG, Nicod P, Brunner HR. Clinical studies with a vascular vasopressin antagonist. J Cardiovasc Pharmacol. 1986;8(Suppl 7):S111–6.

    Article  CAS  PubMed  Google Scholar 

  28. Gross F. Renin and hypertension, physiological or pathological agents? Klin Wochenschr. 1958;36:693–706.

    Article  CAS  PubMed  Google Scholar 

  29. Weir MR, Dzau VJ. The renin-angiotensin-aldosterone system: a specific target for hypertension management. Am J Hypertens. 1999;12(12 Pt 3):205–13.

    Article  Google Scholar 

  30. Tomaschitz A, Pilz S, Ritz E, Obermayer-Pietsch B, Pieber TR. Aldosterone and arterial hypertension. Nat Rev Endocrinol. 2010;6:83–93.

    Article  CAS  PubMed  Google Scholar 

  31. Vasan RS, Evans JC, Larson MG, Wilson PWF, Meigs JB, Rifai N, et al. Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N Engl J Med. 2004;351:33–41.

    Article  CAS  PubMed  Google Scholar 

  32. Connell JMC, Davies E. The new biology of aldosterone. J Endocrinol. 2005;186(1):1–20.

    Article  CAS  PubMed  Google Scholar 

  33. Schrier RW, Masoumi A, Elhassan E. Aldosterone: role in edematous disorders, hypertension, chronic renal failure, and metabolic syndrome. Clin J Am Soc Nephrol. 2010;5:1132–40.

    Article  CAS  PubMed  Google Scholar 

  34. Briet M, Schiffrin EL. Treatment of arterial remodeling in essential hypertension. Curr Hypertens Rep. 2013;15:3–9.

    Article  CAS  PubMed  Google Scholar 

  35. Lemarié CA, Paradis P, Schiffrin EL. New insights on signaling cascades induced by cross talk between angiotensin II and aldosterone. J Mol Med. 2008;86:673–8.

    Article  CAS  PubMed  Google Scholar 

  36. Baumann M, Megens R, Bartholome R, Dolff S, van Zandvoort M, Smits J, Sruijker-Boudier HA, De Mey J. Prehypertensive renin-angiotensin-aldosterone system blockade in spontaneously hypertensive rats ameliorates the loss of long-term vascular function. Hypertens Res. 2007;30:853–61.

    Article  CAS  PubMed  Google Scholar 

  37. Unger T, Steckelings UM, dos Santos RAS, editors. The protective arm of the renin angiotensin system—functional aspects and therapeutic implications. 1st ed. London: Academic Press, Elsevier; 2015.

    Google Scholar 

  38. Iwai M, Horiuchi M. Devil and angel in the renin-angiotensin system: ACE-angiotensin II AT1 receptor axis vs. ACE2 angiotensin-(1-7)-Mas receptor axis. Hypertens Res. 2009;32:533–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Rentzsch B, Todiras M, Iliescu R, Popova E, Campos LA, Oliveira ML, et al. Transgenic angiotensin-converting enzyme 2 overexpression in vessels of SHRSP rats reduces blood pressure and improves endothelial function. Hypertension. 2008;52:967–73.

    Article  CAS  PubMed  Google Scholar 

  40. Santos RA, Ferreira AJ, Verano-Braga T, Bader M. Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: new players of the renin-angiotensin system. J Endocrinol. 2013;216:R1–R17.

    Article  CAS  PubMed  Google Scholar 

  41. Sampaio WO, Souza dos Santos RA, Faria-Silva R, da 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.

    Article  CAS  PubMed  Google Scholar 

  42. Bodiga S, Zhong JC, Wang W, Basu R, Lo J, Liu GC, et al. Enhanced susceptibility to biomechanical stress in ACE2 null mice is prevented by loss of the p47(phox) NADPH oxidase subunit. Cardiovasc Res. 2011;91:151–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Durik M, Sevá Pessôa B, Roks AJ. The renin-angiotensin system, bone marrow and progenitor cells. Clin Sci (Lond). 2012;123:205–23.

    Article  CAS  Google Scholar 

  44. Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, de Buhr I, et al. Angiotensin-(1–7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003;100:8258–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kostenis E, Milligan G, Christopoulos A, Sanchez-Ferrer CF, Heringer-Walther S, Sexton PM, et al. G-protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor. Circulation. 2005;111:1806–13.

    Article  CAS  PubMed  Google Scholar 

  46. Villela D, Leonhardt J, Patel N, Joseph J, Kirsch S, Hallberg A, et al. Angiotensin type 2 receptor (AT2R) and receptor Mas: a complex liaison. Clin Sci. 2015;128:227–34.

    Article  CAS  Google Scholar 

  47. Singh Y, Singh K, Sharma PL. Effect of combination of renin inhibitor and Mas-receptor agonist in DOCA-salt-induced hypertension in rats. Mol Cell Biochem. 2013;373:189–94.

    Article  CAS  PubMed  Google Scholar 

  48. Patel JM, Martens JR, Li YD, Gelband CH, Raizada MK, Block ER. Angiotensin IV receptor-mediated activation of lung endothelial NOS is associated with vasorelaxation. Am J Physiol. 1998;275(6 Pt 1):L1061–8.

    CAS  PubMed  Google Scholar 

  49. Vinh A, Widdop RE, Drummond GR, Gaspari TA. Chronic angiotensin IV treatment reverses endothelial dysfunction in ApoE-deficient mice. Cardiovasc Res. 2008;77:178–87.

    Article  CAS  PubMed  Google Scholar 

  50. De Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev. 2000;52:415–72.

    PubMed  Google Scholar 

  51. Zhang H, Han GW, Batyuk A, Ishchenko A, White KL, Patel N, et al. Structural basis for selectivity and diversity in angiotensin II receptors. Nature. 2017;544:327–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Gohlke P, Pees C, Unger T. AT2 receptor stimulation increases aortic cyclic GMP in SHRSP by a kinin-dependent mechanism. Hypertension. 1998;31:349–55.

    Article  CAS  PubMed  Google Scholar 

  53. Fischer TA, Singh K, O’Hara DS, Kaye DM, Kelly RA. Role of AT1 and AT2 receptors in regulation of MAPKs and MKP-1 by ANG II in adult cardiac myocytes. Am J Physiol. 1998;275:H906–16.

    CAS  PubMed  Google Scholar 

  54. Nouet S, Nahmias C. Signal transduction from the angiotensin II AT2 receptor. Trends Endocrinol Metab. 2000;11:1–6.

    Article  CAS  PubMed  Google Scholar 

  55. AbdAlla S, Lother H, Abdel-tawab AM, Quitterer U. The angiotensin II AT2 receptor is an AT1 receptor antagonist. J Biol Chem. 2001;276:39721–6.

    Article  CAS  PubMed  Google Scholar 

  56. Gao J, Zhang H, Le KD, Chao J, Gao L. Activation of central angiotensin type 2 receptors suppresses norepinephrine excretion and blood pressure in conscious rats. Am J Hypertens. 2011;24:724–30.

    Article  CAS  PubMed  Google Scholar 

  57. Inagami T, Eguchi S, Numaguchi K, Motley ED, Tang H, Matsumoto T, Yamakawa T. Cross-talk between angiotensin II receptors and the tyrosine kinases and phosphatases. J Am Soc Nephrol. 1999;10(Suppl 11):S57–61.

    CAS  PubMed  Google Scholar 

  58. Wiemer G, Schölkens BA, Wagner A, Heitsch H, Linz W. The possible role of angiotensin II subtype AT2 receptors in endothelial cells and isolated ischemic rat hearts. J Hypertens Suppl. 1993;11:S234–5.

    Article  CAS  PubMed  Google Scholar 

  59. Liu YH, Yang XP, Sharov VG, Nass O, Sabbah HN, Peterson E, Carretero OA. Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors. J Clin Invest. 1997;99:1926–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kraehling JR, Sessa WC. Contemporary approaches to modulating the nitric oxide-cGMP pathway in cardiovascular disease. Circ Res. 2017;120:1174–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Siragy HM, Inagami T, Ichiki T, Carey RM. Sustained hypersensitivity to angiotensin II and its mechanism in mice lacking the subtype-2 (AT2) angiotensin receptor. Proc Natl Acad Sci U S A. 1999;96:6506–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Tsutsumi Y, Matsubara H, Masaki H, Kurihara H, Murasawa S, Takai S, et al. Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation. J Clin Invest. 1999;104:925–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Batenburg WW, Garrelds IM, Bernasconi CC, Juillerat-Jeanneret L, van Kats JP, Saxena PR, Danser AH. Angiotensin II type 2 receptor-mediated vasodilation in human coronary microarteries. Circulation. 2004;109:2296–301.

    Article  CAS  PubMed  Google Scholar 

  64. Savoia C, Touyz RM, Volpe M, Schiffrin EL. Angiotensin type 2 receptor in resistance arteries of type 2 diabetic hypertensive patients. Hypertension. 2007;49:341–6.

    Article  CAS  PubMed  Google Scholar 

  65. Widdop RE, Jones ES, Hannan RE, Gaspari TA. Angiotensin AT2 receptors: cardiovascular hope or hype? Br J Pharmacol. 2003;140:809–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Steckelings UM, Paulis L, Namsolleck P, Unger T. AT2 receptor agonists: hypertension and beyond. Curr Opin Nephrol Hypertens. 2012;21:142–6.

    Article  CAS  PubMed  Google Scholar 

  67. Wan Y, Wallinder C, Plouffe B, Beaudry H, Mahalingam AK, Wu X, et al. Design, synthesis, and biological evaluation of the first selective nonpeptide AT2 receptor agonist. J Med Chem. 2004;47:5995–6008.

    Article  CAS  PubMed  Google Scholar 

  68. Paulis L, Becker STR, Lucht K, Schwengel K, Slavic S, Kaschina E, et al. Direct angiotensin II type 2 receptor stimulation in Nω-nitro-L-arginine-methyl ester-induced hypertension: the effect on pulse wave velocity and aortic remodeling. Hypertension. 2012;59:485–92.

    Article  CAS  PubMed  Google Scholar 

  69. Rehman A, Leibowitz A, Yamamoto N, Rautureau Y, Paradis P, Schiffrin EL. Angiotensin type 2 receptor agonist compound 21 reduces vascular injury and myocardial fibrosis in stroke-prone spontaneously hypertensive rats. Hypertension. 2012;59(2):291–9.

    Article  CAS  PubMed  Google Scholar 

  70. Hrenák J, Arendášová K, Rajkovičová R, Aziriová S, Repová K, Krajčírovičová K, et al. Protective effect of captopril, olmesartan, melatonin and compound 21 on doxorubicin-induced nephrotoxicity in rats. Physiol Res. 2013;62(Suppl 1):S181–9.

    PubMed  Google Scholar 

  71. Matavelli LC, Huang J, Siragy HM. Angiotensin AT2 receptor stimulation inhibits early renal inflammation in renovascular hypertension. Hypertension. 2011;57:308–13.

    Article  CAS  PubMed  Google Scholar 

  72. Begorre MA, Dib A, Habchi K, Guihot AL, Bourreau J, Vessieres E, et al. Microvascular vasodilator properties of the angiotensin 2 receptor in a mouse model of type 1 diabetes. Sci Rep. 2017;7:45625.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Sales VL, Sukhova GK, Lopez-Ilasaca MA, Libby P, Dzau VJ, Pratt RE. Angiotensin type 2 receptor is expressed in murine atherosclerotic lesions and modulates lesion evolution. Circulation. 2005;112:3328–36.

    Article  CAS  PubMed  Google Scholar 

  74. Nakajima M, Hutchinson HG, Fujinaga M, Hayashida W, Morishita R, Zhang L, et al. The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: gain-of-function study using gene transfer. Proc Natl Acad Sci U S A. 1995;92:10663–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Iwai M, Chen R, Li Z, Shiuchi T, Suzuki J, Ide A, et al. Deletion of angiotensin II type 2 receptor exaggerated atherosclerosis in apolipoprotein E-null mice. Circulation. 2005;112:1636–43.

    Article  CAS  PubMed  Google Scholar 

  76. Kaschina E, Scholz H, Steckelings UM, Sommerfeld M, Kemnitz UR, Artuc M, Schmidt S, Unger T. Transition from atherosclerosis to aortic aneurysm in humans coincides with an increased expression of RAS components. Atherosclerosis. 2009;205:396–403.

    Article  CAS  PubMed  Google Scholar 

  77. Meltzer JI. A specialist in clinical hypertension critiques the TROPHY trial. Am J Hypertens. 2006;19:1098–100.

    Article  PubMed  Google Scholar 

  78. Julius S, Kaciroti N, Egan BM, Nesbitt S, Michelson EL. Trial of Preventing Hypertension (TROPHY) Investigators. TROPHY study: outcomes based on the Seventh Report of the Joint National Committee on Hypertension definition of hypertension. J Am Soc Hypertens. 2008;2:39–43.

    Article  PubMed  Google Scholar 

  79. Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004;363(9426):2022–31.

    Article  CAS  PubMed  Google Scholar 

  80. Kjeldsen SE, Narkiewicz K, Hedner T. An American TROPHY in the prevention of hypertension. Blood Press. 2006;15:132–4.

    Article  PubMed  Google Scholar 

  81. Qureshi AI, Suri MF, Kirmani JF, Divani AA. Prevalence and trends of prehypertension and hypertension in United States: National Health and Nutrition Examination Surveys 1976 to 2000. Mred Sci Monit. 2005;11:CR403–9.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Cardiovascular Research (CCR), Charité—Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Pharmacology, Berlin, Germany

    Elena Kaschina

  2. CARIM—School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands

    Thomas Unger

Authors
  1. Elena Kaschina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Unger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Unger .

Editor information

Editors and Affiliations

  1. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Reuven Zimlichman

  2. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

    Stevo Julius

  3. Emeritus Professor of Medicine, University of Milano-Bicocca, Milan, Italy

    Giuseppe Mancia

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kaschina, E., Unger, T. (2019). Prehypertension and the Renin-Angiotensin-Aldosterone System. In: Zimlichman, R., Julius, S., Mancia, G. (eds) Prehypertension and Cardiometabolic Syndrome. Updates in Hypertension and Cardiovascular Protection. Springer, Cham. https://doi.org/10.1007/978-3-319-75310-2_22

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-75310-2_22

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-75309-6

  • Online ISBN: 978-3-319-75310-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation