Advertisement

Angiotensin Converting Enzyme Inhibitors and AT1 Antagonists for Treatment of Hypertension

Chapter
  • 1.2k Downloads
Part of the Current Cardiovascular Therapy book series (CCT, volume 5)

Abstract

Essential hypertension is the major cardiovascular risk factor. The main objective of treatment of essential hypertension is represented by long-term reduction of cardiovascular (CV) risk. This goal can be achieved through the control of blood pressure (BP) values, the prevention of hypertension-related target organ damage (TOD) and metabolic complication, and reduction of CV events. During the last 25 years has emerged that the dysregulation of rennin-angiotensin-system (RAS) plays a pivotal role not only in the genesis of hypertension, but also in the development of TOD, diabetes, obesity, atherosclerosis and their complications. In fact, it has been documented that angiotensin II (Ang II), the effector of RAS, is involved in the regulation of endothelial function, tissue remodeling, inflammation, oxidative stress, differentiation of adipocytes, glucose metabolism and electrolytes homeostasis. Therefore, it does not surprise if the principal interventional trials have demonstrated that the blocking of the RAS, obtained either with angiotensin converting enzyme (ACE)-inhibitors, or with the type 1 Ang II (AT1) receptors blockers (ARBs), reduce the incidence of CV events in hypertensive and high CV risk patients. ACE-inhibitors block the conversion of angiotensin-I into Ang II reducing the circulating and local levels of Ang II. ACE-inhibitors also reduce the release of aldosterone and vasopressin, decrease the activity of sympathetic nervous system, as well as the trophic effects of Ang II on cardiac muscle and vessels. The inhibition of ACE produces also an increase in plasma bradykinin levels, which in turn, stimulates the type 2 bradykinin (B2) receptors leading to the release of nitric oxide (NO), and vasoactive prostaglandins (prostacyclin and prostaglandin E2). These biological effects are translated in several pharmacological actions consisting in the reduction of BP, in the decrease of plasma levels of epinephrine, norepinephrine and vasopressin, in the interference with development of vascular and cardiac hypertrophy and extracellular matrix proliferation, in the decrease renal vascular resistances and increase renal blood flow, which in turn, promotes Na+ and water excretion, in the modulation of fibrinolytic balance resulting in antithrombotic effect.

Keywords

ACE ACEi Hypertension AT1 AT1 Antagonists RAS Ang II Cardiovascular ARBs 

References

  1. 1.
    Abuissa H, Jones PG, Marso SP, et al. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials. J Am Coll Cardiol. 2005;46(5):821–6.PubMedGoogle Scholar
  2. 2.
    Ailhaud G. Cross talk between adipocytes and their precursors: relationships with adipose tissue development and blood pressure. Ann N Y Acad Sci. 1999;892:127–33.PubMedGoogle Scholar
  3. 3.
    Andersson P, Cederholm T, Johansson AS, et al. Captopril-impaired production of tumor necrosis factor-alpha-induced interleukin-1beta in human monocytes is associated with altered intracellular distribution of nuclear factor-kappaB. J Lab Clin Med. 2002;140(2):103–9.PubMedGoogle Scholar
  4. 4.
    Arbin V, Claperon N, Fournie-Zaluski MC, et al. Acute effect of the dual angiotensin-converting enzyme and neutral endopeptidase 24–11 inhibitor mixanpril on insulin sensitivity in obese Zucker rat. Br J Pharmacol. 2001;133(4):495–502.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Baguet JP, Asmar R, Valensi P, et al. Effects of candesartan cilexetil on carotid remodeling in hypertensive diabetic patients: the MITEC study. Vasc Health Risk Manag. 2009;5(1):175–83.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Bähr IN, Tretter P, Krüger J, et al. High-dose treatment with telmisartan induces monocytic peroxisome proliferator-activated receptor-γ target genes in patients with the metabolic syndrome. Hypertension. 2011;58(4):725–32.PubMedGoogle Scholar
  7. 7.
    Bendall JK, Cave AC, Heymes C, et al. Pivotal role of a gp91(phox)-containing NADPH oxidase in angiotensin II-induced cardiac hypertrophy in mice. Circulation. 2002;105(3):293–6.PubMedGoogle Scholar
  8. 8.
    Benndorf R, Böger RH, Ergün S, et al. Angiotensin II type 2 receptor inhibits vascular endothelial growth factor-induced migration and in vitro tube formation of human endothelial cells. Circ Res. 2003;93(5):438–47.PubMedGoogle Scholar
  9. 9.
    Bruckschlegel G, Holmer SR, Jandeleit K, et al. Blockade of the renin-angiotensin system in cardiac pressure-overload hypertrophy in rats. Hypertension. 1995;25(2):250–9.PubMedGoogle Scholar
  10. 10.
    Carlsson PO, Berne C, Jansson L. Angiotensin II and the endocrine pancreas: effects on islet blood flow and insulin secretion in rats. Diabetologia. 1998;41(2):127–33.PubMedGoogle Scholar
  11. 11.
    Carvalho CR, Thirone AC, Gontijo JA, et al. Effect of captopril, losartan, and bradykinin on early steps of insulin action. Diabetes. 1997;46(12):1950–7.PubMedGoogle Scholar
  12. 12.
    Catapano F, Chiodini P, De Nicola L, et al. Antiproteinuric response to dual blockade of the renin-angiotensin system in primary glomerulonephritis: meta-analysis and metaregression. Am J Kidney Dis. 2008;52(3):475–85.PubMedGoogle Scholar
  13. 13.
    Chobanian AV, Haudenschild CC, Nickerson C, et al. Trandolapril inhibits atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Hypertension. 1992;20(4):473–7.PubMedGoogle Scholar
  14. 14.
    Chrysant SG. The role of angiotensin II receptors in stroke protection. Curr Hypertens Rep. 2012;14(3):202–8.PubMedGoogle Scholar
  15. 15.
    Conlin PR, Spence JD, Williams B, et al. Angiotensin II antagonists for hypertension: are there differences in efficacy? Am J Hypertens. 2000;13(4 Pt 1):418–26.PubMedGoogle Scholar
  16. 16.
    D’Amore A, Black MJ, Thomas WG. The angiotensin II type 2 receptor causes constitutive growth of cardiomyocytes and does not antagonize angiotensin II type 1 receptor-mediated hypertrophy. Hypertension. 2005;46(6):1347–54.PubMedGoogle Scholar
  17. 17.
    Dahlöf 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(9311):995–1003.PubMedGoogle Scholar
  18. 18.
    Dal Ponte DB, Fogt DL, Jacob S, et al. Interactions of captopril and verapamil on glucose tolerance and insulin action in an animal model of insulin resistance. Metabolism. 1998;47(8):982–7.PubMedGoogle Scholar
  19. 19.
    Daugherty A, Rateri DL, Lu H, et al. Hypercholesterolemia stimulates angiotensin peptide synthesis and contributes to atherosclerosis through the AT1A receptor. Circulation. 2004;110(25):3849–57.PubMedGoogle Scholar
  20. 20.
    Engeli S, Sharma AM. Role of adipose tissue for cardiovascular-renal regulation in health and disease. Horm Metab Res. 2000;32(11–12):485–99.PubMedGoogle Scholar
  21. 21.
    Fagard RH, Celis H, Thijs L, et al. Regression of left ventricular mass by antihypertensive treatment: a meta-analysis of randomized comparative studies. Hypertension. 2009;54(5):1084–91.PubMedGoogle Scholar
  22. 22.
    Fernandez LA, Caride VJ, Strömberg C, et al. Angiotensin AT2 receptor stimulation increases survival in gerbils with abrupt unilateral carotid ligation. J Cardiovasc Pharmacol. 1994;24(6):937–40.PubMedGoogle Scholar
  23. 23.
    Ferrario CM, Strawn WB. Targeting the RAAS for the treatment of atherosclerosis. Drug Discov Today Ther Strat. 2005;2(3):221–9.Google Scholar
  24. 24.
    Fryer LG, Hajduch E, Rencurel F, et al. Activation of glucose transport by AMP-activated protein kinase via stimulation of nitric oxide synthase. Diabetes. 2000;49(12):1978–85.PubMedGoogle Scholar
  25. 25.
    Gorzelniak K, Engeli S, Janke J, et al. Hormonal regulation of the human adipose-tissue renin-angiotensin system: relationship to obesity and hypertension. J Hypertens. 2002;20(5):965–73.PubMedGoogle Scholar
  26. 26.
    Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet. 2003;362(9386):772–6.PubMedGoogle Scholar
  27. 27.
    Grassi G, Seravalle G, Dell’Oro R, et al. Comparative effects of candesartan and hydrochlorothiazide on blood pressure, insulin sensitivity, and sympathetic drive in obese hypertensive individuals: results of the CROSS study. J Hypertens. 2003;21(9):1761–9.PubMedGoogle Scholar
  28. 28.
    Gruppo Italiano di Studi Epidemiologici in Nefrologia. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet. 1997;349(9069):1857–63.Google Scholar
  29. 29.
    Hansson L, Lindholm LH, Ekbom T, et al. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study. Lancet. 1999;354(9192):1751–6.PubMedGoogle Scholar
  30. 30.
    Hansson L, Lindholm LH, Niskanen L, et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet. 1999;353(9153):611–6.PubMedGoogle Scholar
  31. 31.
    Henriksen EJ, Jacob S. Effects of captopril on glucose transport activity in skeletal muscle of obese Zucker rats. Metabolism. 1995;44(2):267–72.PubMedGoogle Scholar
  32. 32.
    Hirohata A, Yamamoto K, Miyoshi T, et al. Impact of olmesartan on progression of coronary atherosclerosis a serial volumetric intravascular ultrasound analysis from the OLIVUS (impact of OLmesarten on progression of coronary atherosclerosis: evaluation by intravascular ultrasound) trial. J Am Coll Cardiol. 2010;55(10):976–82.PubMedGoogle Scholar
  33. 33.
    Ichihara S, Senbonmatsu T, Price Jr E, et al. Angiotensin II type 2 receptor is essential for left ventricular hypertrophy and cardiac fibrosis in chronic angiotensin II-induced hypertension. Circulation. 2001;104(3):346–51.PubMedGoogle Scholar
  34. 34.
    Iino Y, Hayashi M, Kawamura T, et al. Renoprotective effect of losartan in comparison to amlodipine in patients with chronic kidney disease and hypertension – a report of the Japanese Losartan Therapy Intended for the Global Renal Protection in Hypertensive Patients (JLIGHT) study. Hypertens Res. 2004;27(1):21–30.PubMedGoogle Scholar
  35. 35.
    ONTARGET Investigators, Yusuf S, Teo KK, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547–59.Google Scholar
  36. 36.
    Jacob S, Henriksen EJ, Fogt DL, et al. Effects of trandolapril and verapamil on glucose transport in insulin-resistant rat skeletal muscle. Metabolism. 1996;45(5):535–41.PubMedGoogle Scholar
  37. 37.
    Jafar TH, Schmid CH, Landa M, et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. Ann Intern Med. 2001;135(2):73–87.PubMedGoogle Scholar
  38. 38.
    Jafar TH, Stark PC, Schmid CH, et al. Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease. Kidney Int. 2001;60(3):1131–40.PubMedGoogle Scholar
  39. 39.
    Jones BH, Standridge MK, Taylor JW, et al. Angiotensinogen gene expression in adipose tissue: analysis of obese models and hormonal and nutritional control. Am J Physiol. 1997;273(1 Pt 2):R236–42.PubMedGoogle Scholar
  40. 40.
    Julius S, Kjeldsen SE, Weber M, 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.PubMedGoogle Scholar
  41. 41.
    Kanome T, Watanabe T, Nishio K, et al. Angiotensin II upregulates acyl-CoA: cholesterol acyltransferase-1 via the angiotensin II Type 1 receptor in human monocyte-macrophages. Hypertens Res. 2008;31(9):1801–10.PubMedGoogle Scholar
  42. 42.
    Keidar S, Kaplan M, Hoffman A, et al. Angiotensin II stimulates macrophage-mediated oxidation of low density lipoproteins. Atherosclerosis. 1995;115(2):201–15.PubMedGoogle Scholar
  43. 43.
    Kim MP, Zhou M, Wahl LM. Angiotensin II increases human monocyte matrix metalloproteinase-1 through the AT2 receptor and prostaglandin E2: implications for atherosclerotic plaque rupture. J Leukoc Biol. 2005;78(1):195–201.PubMedGoogle Scholar
  44. 44.
    Klingbeil AU, Schneider M, Martus P, et al. A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension. Am J Med. 2003;115(1):41–6.PubMedGoogle Scholar
  45. 45.
    Koh KK, Han SH, Chung WJ, et al. Comparison of effects of losartan, irbesartan, and candesartan on flow-mediated brachial artery dilation and on inflammatory and thrombolytic markers in patients with systemic hypertension. Am J Cardiol. 2004;93(11):1432–5, A10.PubMedGoogle Scholar
  46. 46.
    Kojima M, Shiojima I, Yamazaki T, et al. Angiotensin II receptor antagonist TCV-116 induces regression of hypertensive left ventricular hypertrophy in vivo and inhibits the intracellular signaling pathway of stretch-mediated cardiomyocyte hypertrophy in vitro. Circulation. 1994;89(5):2204–11.PubMedGoogle Scholar
  47. 47.
    Krikov M, Thone-Reineke C, Müller S, et al. Candesartan but not ramipril pretreatment improves outcome after stroke and stimulates neurotrophin BNDF/TrkB system in rats. J Hypertens. 2008;26(3):544–52.PubMedGoogle Scholar
  48. 48.
    Kshirsagar AV, Joy MS, Hogan SL, et al. Effect of ACE inhibitors in diabetic and nondiabetic chronic renal disease: a systematic overview of randomized placebo-controlled trials. Am J Kidney Dis. 2000;35(4):695–707.PubMedGoogle Scholar
  49. 49.
    Kunz R, Friedrich C, Wolbers M, et al. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med. 2008;148(1):30–48.PubMedGoogle Scholar
  50. 50.
    Kyvelou SM, Vyssoulis GP, Karpanou EA, et al. Effects of antihypertensive treatment with angiotensin II receptor blockers on lipid profile: an open multi-drug comparison trial. Hellenic J Cardiol. 2006;47(1):21–8.PubMedGoogle Scholar
  51. 51.
    Lau DC, Dhillon B, Yan H, et al. Adipokines: molecular links between obesity and atheroslcerosis. Am J Physiol Heart Circ Physiol. 2005;288(5):H2031–41.PubMedGoogle Scholar
  52. 52.
    Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903–13.PubMedGoogle Scholar
  53. 53.
    Li J, Culman J, Hörtnagl H, et al. Angiotensin AT2 receptor protects against cerebral ischemia-induced neuronal injury. FASEB J. 2005;19(6):617–9.PubMedGoogle Scholar
  54. 54.
    Li D, Saldeen T, Romeo F, et al. Oxidized LDL upregulates angiotensin II type 1 receptor expression in cultured human coronary artery endothelial cells: the potential role of transcription factor NF-kappaB. Circulation. 2000;102(16):1970–6.PubMedGoogle Scholar
  55. 55.
    Lindholm LH, Persson M, Alaupovic P, et al. Metabolic outcome during 1 year in newly detected hypertensives: results of the Antihypertensive Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation (ALPINE study). J Hypertens. 2003;21(8):1563–74.PubMedGoogle Scholar
  56. 56.
    Linz W, Jessen T, Becker RH, et al. Long-term ACE inhibition doubles lifespan of hypertensive rats. Circulation. 1997;96(9):3164–72.PubMedGoogle Scholar
  57. 57.
    Lonn E, Yusuf S, Dzavik V, et al. Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Circulation. 2001;103(7):919–25.PubMedGoogle Scholar
  58. 58.
    Lu GC, Cheng JW, Zhu KM, et al. A systematic review of angiotensin receptor blockers in preventing stroke. Stroke. 2009;40(12):3876–8.PubMedGoogle Scholar
  59. 59.
    Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC 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). Eur Heart J. 2013;34(28):2159–219.PubMedGoogle Scholar
  60. 60.
    Martinez-Martin FJ, Rodriguez-Rosas H, Peiro-Martinez I, et al. Olmesartan/amlodipine vs olmesartan/hydrochlorothiazide in hypertensive patients with metabolic syndrome: the OLAS study. J Hum Hypertens. 2011;25(6):346–53.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Morel Y, Gadient A, Keller U, et al. Insulin sensitivity in obese hypertensive dyslipidemic patients treated with enalapril or atenolol. J Cardiovasc Pharmacol. 1995;26(2):306–11.PubMedGoogle Scholar
  62. 62.
    Nakao N, Yoshimura A, Morita H, et al. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet. 2003;361(9352):117–24.PubMedGoogle Scholar
  63. 63.
    Nakayama M, Yan X, Price RL, et al. Chronic ventricular myocyte-specific overexpression of angiotensin II type 2 receptor results in intrinsic myocyte contractile dysfunction. Am J Physiol Heart Circ Physiol. 2005;288(1):H317–27.PubMedGoogle Scholar
  64. 64.
    Nickenig G, Sachinidis A, Michaelsen F, et al. Upregulation of vascular angiotensin II receptor gene expression by low-density lipoprotein in vascular smooth muscle cells. Circulation. 1997;95(2):473–8.PubMedGoogle Scholar
  65. 65.
    Nishida Y, Takahashi Y, Nakayama T, et al. Effect of candesartan monotherapy on lipid metabolism in patients with hypertension: a retrospective longitudinal survey using data from electronic medical records. Cardiovasc Diabetol. 2010;9:38.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Olsen MH, Wachtell K, Beevers G, et al. Effects of losartan compared with atenolol on lipids in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension study. Effects of losartan compared with atenolol on lipids in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension study. J Hypertens. 2009;27(3):567–74.PubMedGoogle Scholar
  67. 67.
    Parhofer KG, Münzel F, Krekler M. Effect of the angiotensin receptor blocker irbesartan on metabolic parameters in clinical practice: the DO-IT prospective observational study. Cardiovasc Diabetol. 2007;6:36.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Pollare T, Lithell H, Berne C. A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. N Engl J Med. 1998;321(13):868–73.Google Scholar
  69. 69.
    Putnam K, Shoemaker R, Yiannikouris F, et al. The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome. Am J Physiol Heart Circ Physiol. 2012;302(6):H1219–30.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Reboldi G, Angeli F, Cavallini C, et al. Comparison between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the risk of myocardial infarction, stroke and death: a meta-analysis. J Hypertens. 2008;26(7):1282–9.PubMedGoogle Scholar
  71. 71.
    Reisin E, Weir MR, Falkner B, et al. Lisinopril versus hydrochlorothiazide in obese hypertensive patients: a multicenter placebo-controlled trial. Treatment in Obese Patients With Hypertension (TROPHY) Study Group. Hypertension. 1997;30(1 Pt 1):140–5.PubMedGoogle Scholar
  72. 72.
    Rett K, Wicklmayr M, Dietze GJ, et al. Insulin-induced glucose transporter (GLUT1 and GLUT4) translocation in cardiac muscle tissue is mimicked by bradykinin. Diabetes. 1996;45 Suppl 1:S66–9.PubMedGoogle Scholar
  73. 73.
    Rosei EA, Rizzoni D, Muiesan ML, et al. Effects of candesartan cilexetil and enalapril on inflammatory markers of atherosclerosis in hypertensive patients with non-insulin-dependent diabetes mellitus. J Hypertens. 2005;23(2):435–44.PubMedGoogle Scholar
  74. 74.
    Rotimi C, Cooper R, Ogunbiyi O, et al. Hypertension, serum angiotensinogen, and molecular variants of the angiotensinogen gene among Nigerians. Circulation. 1997;95(10):2348–50.PubMedGoogle Scholar
  75. 75.
    Ruiz-Ortega M, Lorenzo O, Suzuki Y, et al. Proinflammatory actions of angiotensins. Curr Opin Nephrol Hypertens. 2001;10(3):321–9.PubMedGoogle Scholar
  76. 76.
    Ruschitzka F, Taddei S. Angiotensin-converting enzyme inhibitors: first-line agents in cardiovascular protection? Eur Heart J. 2012;33(16):1996–8.PubMedGoogle Scholar
  77. 77.
    Sadoshima J, Izumo S. Molecular characterization of angiotensin II – induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype. Circ Res. 1993;73(3):413–23.PubMedGoogle Scholar
  78. 78.
    Sadoshima J, Izumo S. The cellular and molecular response of cardiac myocytes to mechanical stress. Annu Rev Physiol. 1997;59:551–71.PubMedGoogle Scholar
  79. 79.
    Sadoshima J, Xu Y, Slayter HS, et al. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell. 1993;75(5):977–84.PubMedGoogle Scholar
  80. 80.
    Schmieder RE, Hilgers KF, Schlaich MP, et al. Renin-angiotensin system and cardiovascular risk. Lancet. 2007;369(9568):1208–19.PubMedGoogle Scholar
  81. 81.
    Schmieder RE, Martus P, Klingbeil A. Reversal of left ventricular hypertrophy in essential hypertension. A meta-analysis of randomized double-blind studies. JAMA. 1996;275(19):1507–13.PubMedGoogle Scholar
  82. 82.
    Schupp M, Janke J, Clasen R, et al. Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity. Circulation. 2004;109(17):2054–7.PubMedGoogle Scholar
  83. 83.
    Senbonmatsu T, Ichihara S, Price Jr E, et al. Evidence for angiotensin II type 2 receptor-mediated cardiac myocyte enlargement during in vivo pressure overload. J Clin Invest. 2000;106(3):R25–9.PubMedPubMedCentralGoogle Scholar
  84. 84.
    Sharma AM, Janke J, Gorzelniak K, et al. Angiotensin blockade prevents type 2 diabetes by formation of fat cells. Hypertension. 2002;40(5):609–11.PubMedGoogle Scholar
  85. 85.
    Shiuchi T, Cui TX, Wu L, et al. ACE inhibitor improves insulin resistance in diabetic mouse via bradykinin and NO. Hypertension. 2002;40(3):329–34.PubMedGoogle Scholar
  86. 86.
    Shyu KG, Chen JJ, Shih NL, et al. Angiotensinogen gene expression is induced by cyclical mechanical stretch in cultured rat cardiomyocytes. Biochem Biophys Res Commun. 1995;211(1):241–8.PubMedGoogle Scholar
  87. 87.
    Sola S, Mir MQ, Cheema FA, et al. Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study. Circulation. 2005;111(3):343–8.PubMedGoogle Scholar
  88. 88.
    Sonoda M, Aoyagi T, Takenaka K, et al. A one-year study of the antiatherosclerotic effect of the angiotensin-II receptor blocker losartan in hypertensive patients. A comparison with angiotension-converting enzyme inhibitors. Int Heart J. 2008;49(1):95–103.PubMedGoogle Scholar
  89. 89.
    Steen MS, Foianini KR, Youngblood EB, et al. Interactions of exercise training and ACE inhibition on insulin action in obese Zucker rats. J Appl Physiol. 1999;86(6):2044–51.PubMedGoogle Scholar
  90. 90.
    Stenvinkel P, Andersson P, Wang T, et al. Do ACE-inhibitors suppress tumour necrosis factor-alpha production in advanced chronic renal failure? J Intern Med. 1999;246(5):503–7.PubMedGoogle Scholar
  91. 91.
    Stenvinkel P, Ketteler M, Johnson RJ, et al. IL-10, IL-6, and TNF-alpha: central factors in the altered cytokine network of uremia – the good, the bad, and the ugly. Kidney Int. 2005;67(4):1216–33.PubMedGoogle Scholar
  92. 92.
    Strauss MH, Hall AS. Angiotensin receptor blockers may increase risk of myocardial infarction: unraveling the ARB-MI paradox. Circulation. 2006;114(8):838–54.PubMedGoogle Scholar
  93. 93.
    Suzuki J, Matsubara H, Urakami M, et al. Rat angiotensin II (type 1A) receptor mRNA regulation and subtype expression in myocardial growth and hypertrophy. Circ Res. 1993;73(3):439–47.PubMedGoogle Scholar
  94. 94.
    Suzuki Y, Ruiz-Ortega M, Gomez-Guerrero C, et al. Angiotensin II, the immune system and renal diseases: another road for RAS? Nephrol Dial Transplant. 2003;18(8):1423–6.PubMedGoogle Scholar
  95. 95.
    Taal MW, Brenner BM. Renoprotective benefits of RAS inhibition: from ACEI to angiotensin II antagonists. Kidney Int. 2000;57(5):1803–17.PubMedGoogle Scholar
  96. 96.
    Thoene-Reineke C, Rumschüssel K, Schmerbach K, et al. Prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models. PLoS One. 2011;6(8):e23646. doi: 10.1371/journal.pone.0023646.PubMedPubMedCentralGoogle Scholar
  97. 97.
    Turnbull F, Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003;362(9395):1527–35.PubMedGoogle Scholar
  98. 98.
    Uehara M, Kishikawa H, Isami S, et al. Effect on insulin sensitivity of angiotensin converting enzyme inhibitors with or without a sulphydryl group: bradykinin may improve insulin resistance in dogs and humans. Diabetologia. 1994;37(3):300–7.PubMedGoogle Scholar
  99. 99.
    Vacher E, Richer C, Giudicelli JF. Effects of losartan on cerebral arteries in stroke-prone spontaneously hypertensive rats. J Hypertens. 1996;14(11):1341–8.PubMedGoogle Scholar
  100. 100.
    Vasan RS, Larson MG, Leip EP, et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med. 2001;345(18):1291–7.PubMedGoogle Scholar
  101. 101.
    Verma S, Strauss M. Angiotensin receptor blockers and myocardial infarction. BMJ. 2004;329(7477):1248–9.PubMedPubMedCentralGoogle Scholar
  102. 102.
    Vogt L, Navis G, Köster J, et al. The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial. J Hypertens. 2005;23(11):2055–61.PubMedGoogle Scholar
  103. 103.
    Weinberg EO, Schoen FJ, George D, et al. Angiotensin-converting enzyme inhibition prolongs survival and modifies the transition to heart failure in rats with pressure overload hypertrophy due to ascending aortic stenosis. Circulation. 1994;90(3):1410–22.PubMedGoogle Scholar
  104. 104.
    Yamazaki T, Komuro I, Kudoh S, et al. Angiotensin II partly mediates mechanical stress-induced cardiac hypertrophy. Circ Res. 1995;77(2):258–65.PubMedGoogle Scholar
  105. 105.
    Yusuf S, Sleight P, Pogue J, et al. 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(3):145–53.PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Dipartimento di Scienze Mediche Traslazionali e Dipartimento di Scienze Biomediche AvanzateUniversità FEDERICO II NapoliNaplesItaly

Personalised recommendations