Skip to main content
SpringerLink
Log in

Antihypertensive Drugs and Vascular Health

  • Chapter
  • First Online:
Prehypertension and Cardiometabolic Syndrome

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

  • 711 Accesses

Abstract

Hypertension is a growing health burden and contributes to serious cardiovascular complications from target organ damage. The vascular system is particularly important in patients with elevated blood pressure, because vascular dysfunction is both a cause and consequence of hypertension. Hypertension is characterised by a vascular phenotype of endothelial dysfunction, vascular inflammation, arterial remodelling and increased stiffness. Of the many classes of antihypertensive drugs, those that influence vascular health have the greatest efficacy for reducing cardiovascular risk. Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and calcium channel blockers ameliorate vascular remodelling and improve endothelial function. Mineralocorticoid receptor antagonists reduce arterial stiffness, improve endothelial function and are established antihypertensive drugs, particularly in patients with resistant hypertension. Patients prone to salt-sensitivity benefit from diuretics, which influence salt physiology and balance and reduce arterial stiffness. Not all antihypertensive drugs are vasoprotective. Beta blockers, like atenolol, reduce blood pressure, but do not regress remodelling and fail to improve endothelial function. Selecting and refining the optimum drug therapy for the treatment of hypertension remains the key challenge and should prompt thought about the diverse pathophysiological mechanisms involved. This should always be in association with lifestyle modifications, which remains a cornerstone in preventing and improving vascular changes associated with high blood pressure.

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. Harvey A, Montezano AC, Lopes RA, Rios F, Touyz RM. Vascular fibrosis in aging and hypertension: molecular mechanisms and clinical implications. Can J Cardiol. 2016;32(5):659–68.

    Article  PubMed  Google Scholar 

  2. Touyz RM, Dominiczak AF. Hypertension guidelines: is it time to reappraise blood pressure thresholds and targets? Hypertension. 2016;67(4):688–9.

    Article  CAS  PubMed  Google Scholar 

  3. Taddei S, Virdis A, Ghiadoni L, Sudano I, Salvetti A. Effects of antihypertensive drugs on endothelial dysfunction: clinical implications. Drugs. 2002;62(2):265–84.

    Article  CAS  PubMed  Google Scholar 

  4. Harvey A, Montezano AC, Touyz RM. Vascular biology of ageing—implications in hypertension. J Mol Cell Cardiol. 2015;83(C):112–21.

    Article  CAS  Google Scholar 

  5. Lopes RA, Neves KB, Tostes RC, Montezano AC, Touyz RM. Downregulation of nuclear factor erythroid 2-related factor and associated antioxidant genes contributes to redox-sensitive vascular dysfunction in hypertension. Hypertension. 2015;66(6):1240–50.

    Article  CAS  PubMed  Google Scholar 

  6. AlGhatrif M, Strait JB, Morrell CH, et al. Longitudinal trajectories of arterial stiffness and the role of blood pressure: the Baltimore longitudinal study of aging. Hypertension. 2013;62(5):934–41.

    Article  CAS  PubMed  Google Scholar 

  7. Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a “set up” for vascular disease. Circulation. 2003;107(1):139–46.

    Article  PubMed  Google Scholar 

  8. Lakatta EG. The reality of aging viewed from the arterial wall. Artery Res. 2013;7(2):73–80.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Wind S, Beuerlein K, Armitage ME, et al. Oxidative stress and endothelial dysfunction in aortas of aged spontaneously hypertensive rats by NOX1/2 is reversed by NADPH oxidase inhibition. Hypertension. 2010;56(3):490–7.

    Article  CAS  PubMed  Google Scholar 

  10. Touyz RM, Briones AM, Sedeek M, Burger D, Montezano AC. NOX isoforms and reactive oxygen species in vascular health. Mol Interv. 2011;11(1):27–35.

    Article  CAS  PubMed  Google Scholar 

  11. Montezano AC, Touyz RM. Molecular mechanisms of hypertension--reactive oxygen species and antioxidants: a basic science update for the clinician. Can J Cardiol. 2012;28(3):288–95.

    Article  CAS  PubMed  Google Scholar 

  12. Montezano AC, Burger D, Ceravolo GS, Yusuf H, Montero M, Touyz RM. Novel Nox homologues in the vasculature: focusing on Nox4 and Nox5. Clin Sci. 2011;120(4):131–41.

    Article  CAS  Google Scholar 

  13. Lee MY, Griendling KK. Redox signaling, vascular function, and hypertension. Antioxid Redox Signal. 2008;10(6):1045–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Weinberger MH, Miller JZ, Luft FC, Grim CE, Fineberg NS. Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension. 1986;8(6 Pt 2):II127–34.

    CAS  PubMed  Google Scholar 

  15. Dahl LK, Heine M, Tassinari L. Role of genetic factors in susceptibility to experimental hypertension due to chronic excess salt ingestion. Nature. 1962;194:480–2.

    Article  CAS  PubMed  Google Scholar 

  16. Elijovich F, Weinberger MH, Anderson CAM, et al. Salt sensitivity of blood pressure: a scientific statement from the American Heart Association. Hypertension. 2016;68(3):e7–e46.

    Article  CAS  PubMed  Google Scholar 

  17. Chen PY, Sanders PW. L-arginine abrogates salt-sensitive hypertension in dahl/Rapp rats. J Clin Investig. 1991;88(5):1559–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Feng W, Ying W-Z, Aaron KJ, Sanders PW. Transforming growth factor-β mediates endothelial dysfunction in rats during high salt intake. Am J Physiol Renal Physiol. 2015;309(12):F1018–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Greaney JL, DuPont JJ, Lennon-Edwards SL, Sanders PW, Edwards DG, Farquhar WB. Dietary sodium loading impairs microvascular function independent of blood pressure in humans: role of oxidative stress. J Physiol Lond. 2012;590(21):5519–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nurkiewicz TR, Boegehold MA. High salt intake reduces endothelium-dependent dilation of mouse arterioles via superoxide anion generated from nitric oxide synthase. Am J Physiol Regul Integr Comp Physiol. 2007;292(4):R1550–6.

    Article  CAS  PubMed  Google Scholar 

  21. Raffai G, Durand MJ, Lombard JH. Acute and chronic angiotensin-(1-7) restores vasodilation and reduces oxidative stress in mesenteric arteries of salt-fed rats. Am J Physiol Heart Circ Physiol. 2011;301(4):H1341–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gu JW, Anand V, Shek EW, et al. Sodium induces hypertrophy of cultured myocardial myoblasts and vascular smooth muscle cells. Hypertension. 1998;31(5):1083–7.

    Article  CAS  PubMed  Google Scholar 

  23. Machnik A, Neuhofer W, Jantsch J, et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat Med. 2009;15(5):545–52.

    Article  CAS  PubMed  Google Scholar 

  24. Wiig H, Schröder A, Neuhofer W, et al. Immune cells control skin lymphatic electrolyte homeostasis and blood pressure. J Clin Invest. 2013;123(7):2803–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kopp C, Linz P, Dahlmann A, et al. 23Na magnetic resonance imaging-determined tissue sodium in healthy subjects and hypertensive patients. Hypertension. 2013;61(3):635–40.

    Article  CAS  PubMed  Google Scholar 

  26. Titze J, Luft FC. Speculations on salt and the genesis of arterial hypertension. Kidney Int. 2017;91(6):1324–35.

    Article  CAS  PubMed  Google Scholar 

  27. Laffer CL, Scott RC, Titze JM, Luft FC, Elijovich F. Hemodynamics and salt-and-water balance link sodium storage and vascular dysfunction in salt-sensitive subjects. Hypertension. 2016;68(1):195–203.

    Article  CAS  PubMed  Google Scholar 

  28. Oh YS, Appel LJ, Galis ZS, et al. National Heart, Lung, and Blood Institute working group report on salt in human health and sickness: building on the current scientific evidence. Hypertension. 2016;68(2):281–8.

    Article  CAS  PubMed  Google Scholar 

  29. McMaster WG, Kirabo A, Madhur MS, Harrison DG. Inflammation, immunity, and hypertensive end-organ damage. Circ Res. 2015;116(6):1022–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Schiffrin EL. Immune mechanisms in hypertension and vascular injury. Clin Sci. 2014;126(4):267–74.

    Article  CAS  Google Scholar 

  31. Foss JD, Kirabo A, Harrison DG. Do high-salt microenvironments drive hypertensive inflammation? Am J Physiol Regul Integr Comp Physiol. 2017;312(1):R1–4.

    Article  PubMed  Google Scholar 

  32. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288(5789):373–6.

    Article  CAS  PubMed  Google Scholar 

  33. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327(6122):524–6.

    Article  CAS  PubMed  Google Scholar 

  34. Palmer RMJ, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988;333(6174):664–6.

    Article  CAS  PubMed  Google Scholar 

  35. Bredt DS, Hwang PM, Glatt CE, Lowenstein C, Reed RR, Snyder SH. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature. 1991;351(6329):714–8.

    Article  CAS  PubMed  Google Scholar 

  36. Yanagisawa M, Kurihara H, Kimura S, Goto K, Masaki T. A novel peptide vasoconstrictor, endothelin, is produced by vascular endothelium and modulates smooth muscle Ca2+ channels. J Hypertens Suppl. 1988;6(4):S188–91.

    Article  CAS  PubMed  Google Scholar 

  37. Inoue A, Yanagisawa M, Kimura S, et al. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci U S A. 1989;86(8):2863–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Dharmashankar K, Widlansky ME. Vascular endothelial function and hypertension: insights and directions. Curr Hypertens Rep. 2010;12(6):448–55. https://doi.org/10.1007/s11906-010-0150-2.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Hamburg NM, Benjamin EJ. Assessment of endothelial function using digital pulse amplitude tonometry. Trends Cardiovasc Med. 2009;19(1):6–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Thuillez C, Richard V. Targeting endothelial dysfunction in hypertensive subjects. J Hum Hypertens. 2005;19:S21–5.

    Article  CAS  PubMed  Google Scholar 

  41. Modena MG, Bonetti L, Coppi F, Bursi F, Rossi R. Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women. J Am Coll Cardiol. 2002;40(3):505–10.

    Article  PubMed  Google Scholar 

  42. Benjamin EJ, Larson MG, Keyes MJ, et al. Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham heart study. Circulation. 2004;109(5):613–9.

    Article  PubMed  Google Scholar 

  43. Widlansky ME, Gokce N, Keaney JF, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol. 2003;42(7):1149–60.

    Article  CAS  PubMed  Google Scholar 

  44. Rakova N, Kitada K, Lerchl K, et al. Increased salt consumption induces body water conservation and decreases fluid intake. J Clin Invest. 2017;127(5):1932–43.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Haynes WG, Webb DJ. Endothelin as a regulator of cardiovascular function in health and disease. J Hypertens. 1998;16(8):1081–98.

    Article  CAS  PubMed  Google Scholar 

  46. Schiffrin EL. Role of Endothelin-1 in hypertension. Hypertension. 1999;34(4):876–81.

    Article  CAS  PubMed  Google Scholar 

  47. 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(6):1141–8.

    Article  CAS  PubMed  Google Scholar 

  48. Rajagopalan S, Kurz S, Münzel 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 Investig. 1996;97(8):1916–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Myung S-K, Ju W, Cho B, et al. Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials. BMJ. 2013;346(jan18 1):f10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Radomski MW, Palmer RM, Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet. 1987;2(8567):1057–8.

    Article  CAS  PubMed  Google Scholar 

  51. Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Investig. 1989;83(5):1774–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991;88(11):4651–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. De Caterina R, Libby P, Peng HB, et al. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Investig. 1995;96(1):60–8.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Schiffrin EL. Vascular remodeling in hypertension: mechanisms and treatment. Hypertension. 2012;59(2):367–74.

    Article  CAS  PubMed  Google Scholar 

  55. Savoia C, Sada L, Zezza L, et al. Vascular inflammation and endothelial dysfunction in experimental hypertension. Int J Hypertens. 2011;2011(2 Suppl):1–8.

    Article  Google Scholar 

  56. Blake GJ, Ridker PM. Novel clinical markers of vascular wall inflammation. Circ Res. 2001;89(9):763–71.

    Article  CAS  PubMed  Google Scholar 

  57. Sesso HD, Buring JE, Rifai N, Blake GJ, Gaziano JM, Ridker PM. C-reactive protein and the risk of developing hypertension. JAMA. 2003;290(22):2945–51.

    Article  CAS  PubMed  Google Scholar 

  58. Preston RA, Ledford M, Materson BJ, Baltodano NM, Memon A, Alonso A. Effects of severe, uncontrolled hypertension on endothelial activation: soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1 and von Willebrand factor. J Hypertens. 2002;20(5):871–7.

    Article  CAS  PubMed  Google Scholar 

  59. Blake GJ, Rifai N, Buring JE, Ridker PM. Blood pressure, C-reactive protein, and risk of future cardiovascular events. Circulation. 2003;108(24):2993–9.

    Article  CAS  PubMed  Google Scholar 

  60. Thorand B, Löwel H, Schneider A, et al. C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men: results from the MONICA Augsburg cohort study, 1984–1998. Arch Intern Med. 2003;163(1):93–9.

    Article  CAS  PubMed  Google Scholar 

  61. Van Bortel LM, Laurent S, Boutouyrie P, et al. Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens. 2012;30(3):445–8.

    Article  CAS  PubMed  Google Scholar 

  62. Agnoletti D, Zhang Y, Borghi C, Blacher J, Safar ME. Effects of antihypertensive drugs on central blood pressure in humans: a preliminary observation. Am J Hypertens. 2013;26(8):1045–52.

    Article  CAS  PubMed  Google Scholar 

  63. Mackenzie IS, McEniery CM, Dhakam Z, Brown MJ, Cockcroft JR, Wilkinson IB. Comparison of the effects of antihypertensive agents on central blood pressure and arterial stiffness in isolated systolic hypertension. Hypertension. 2009;54(2):409–13.

    Article  CAS  PubMed  Google Scholar 

  64. Alem M, Milia P, Muir S, Lees K, Walters M. Comparison of the effects of diuretics on blood pressure and arterial stiffness in patients with stroke. J Stroke Cerebrovasc Dis. 2008;17(6):373–7.

    Article  PubMed  Google Scholar 

  65. Safar M, Laurent S, Safavian A, Pannier B, Asmar R. Sodium and large arteries in hypertension. Effects of indapamide. Am J Med. 1988;84(1B):15–9.

    Article  CAS  PubMed  Google Scholar 

  66. Roush GC, Sica DA. Diuretics for hypertension: a review and update. Am J Hypertens. 2016;29(10):1130–7.

    Article  CAS  PubMed  Google Scholar 

  67. Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association professional education Committee of the Council for high blood pressure research. Hypertension. 2008;51(6):1403–19.

    Article  CAS  PubMed  Google Scholar 

  68. Savoia C, Touyz RM, Amiri F, Schiffrin EL. Selective mineralocorticoid receptor blocker eplerenone reduces resistance artery stiffness in hypertensive patients. Hypertension. 2008;51(2):432–9.

    Article  CAS  PubMed  Google Scholar 

  69. Ruilope LM, Redón J, Schmieder R. Cardiovascular risk reduction by reversing endothelial dysfunction: ARBs, ACE inhibitors, or both? Expectations from the ONTARGET trial Programme. Vasc Health Risk Manag. 2007;3(1):1–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Schmieder RE, Delles C, Mimran A, Fauvel JP, Ruilope LM. Impact of telmisartan versus ramipril on renal endothelial function in patients with hypertension and type 2 diabetes. Diabetes Care. 2007;30(6):1351–6.

    Article  CAS  PubMed  Google Scholar 

  71. 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.

    Article  PubMed  Google Scholar 

  72. Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359(23):2417–28.

    Article  CAS  PubMed  Google Scholar 

  73. Hadi HAR, Carr CS, Suwaidi AJ. Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome. Vasc Health Risk Manag. 2005;1(3):183–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Dagenais GR, Yusuf S, Bourassa MG, et al. Effects of ramipril on coronary events in high-risk persons: results of the heart outcomes prevention evaluation study. Circulation. 2001;104(5):522–6.

    Article  CAS  PubMed  Google Scholar 

  75. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The antihypertensive and lipid-lowering treatment to prevent heart attack trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). JAMA. 2002;288(23):2981–97.

    Article  Google Scholar 

  76. Fretheim A, Odgaard-Jensen J, Brørs O, et al. Comparative effectiveness of antihypertensive medication for primary prevention of cardiovascular disease: systematic review and multiple treatments meta-analysis. BMC Med. 2012;10:33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Schiffrin EL. Correction of remodeling and function of small arteries in human hypertension by cilazapril, an angiotensin I-converting enzyme inhibitor. J Cardiovasc Pharmacol. 1996;27(Suppl 2):S13–8.

    Article  CAS  PubMed  Google Scholar 

  78. Schiffrin EL, Deng LY. Comparison of effects of angiotensin I-converting enzyme inhibition and beta-blockade for 2 years on function of small arteries from hypertensive patients. Hypertension. 1995;25(4 Pt 2):699–703.

    Article  CAS  PubMed  Google Scholar 

  79. Rizzoni D, Muiesan ML, Porteri E, et al. Effects of long-term antihypertensive treatment with lisinopril on resistance arteries in hypertensive patients with left ventricular hypertrophy. J Hypertens. 1997;15(2):197–204.

    Article  CAS  PubMed  Google Scholar 

  80. Mancini GB, Henry GC, Macaya C, et al. Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (trial on reversing ENdothelial dysfunction) study. Circulation. 1996;94(3):258–65.

    Article  CAS  PubMed  Google Scholar 

  81. Hornig B, Landmesser U, Kohler C, et al. Comparative effect of ace inhibition and angiotensin II type 1 receptor antagonism on bioavailability of nitric oxide in patients with coronary artery disease: role of superoxide dismutase. Circulation. 2001;103(6):799–805.

    Article  CAS  PubMed  Google Scholar 

  82. Antony I, Lerebours G, Nitenberg A. Angiotensin-converting enzyme inhibition restores flow-dependent and cold pressor test-induced dilations in coronary arteries of hypertensive patients. Circulation. 1996;94(12):3115–22.

    Article  CAS  PubMed  Google Scholar 

  83. Ghiadoni L, Virdis A, Magagna A, Taddei S, Salvetti A. Effect of the angiotensin II type 1 receptor blocker candesartan on endothelial function in patients with essential hypertension. Hypertension. 2000;35(1 Pt 2):501–6.

    Article  CAS  PubMed  Google Scholar 

  84. Taddei S, Virdis A, Ghiadoni L, Mattei P, Salvetti A. Effects of angiotensin converting enzyme inhibition on endothelium-dependent vasodilatation in essential hypertensive patients. J Hypertens. 1998;16(4):447–56.

    Article  CAS  PubMed  Google Scholar 

  85. Ghiadoni L, Magagna A, Versari D, et al. Different effect of antihypertensive drugs on conduit artery endothelial function. Hypertension. 2003;41(6):1281–6.

    Article  CAS  PubMed  Google Scholar 

  86. Dudenbostel T, Glasser SP. Effects of antihypertensive drugs on arterial stiffness. Cardiol Rev. 2012;20(5):259–63.

    Article  PubMed  Google Scholar 

  87. Protogerou AD, Stergiou GS, Vlachopoulos C, Blacher J, Achimastos A. The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part II: evidence for specific class-effects of antihypertensive drugs on pressure amplification. Curr Pharm Des. 2009;15(3):272–89.

    Article  CAS  PubMed  Google Scholar 

  88. Hirata K, Vlachopoulos C, Adji A, O’Rourke MF. Benefits from angiotensin-converting enzyme inhibitor “beyond blood pressure lowering”: beyond blood pressure or beyond the brachial artery? J Hypertens. 2005;23(3):551–6.

    Article  CAS  PubMed  Google Scholar 

  89. 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(5):S234–5.

    Article  CAS  PubMed  Google Scholar 

  90. Maeso R, Navarro-Cid J, Muñoz-García R, et al. Losartan reduces phenylephrine constrictor response in aortic rings from spontaneously hypertensive rats. Role of nitric oxide and angiotensin II type 2 receptors. Hypertension. 1996;28(6):967–72.

    Article  CAS  PubMed  Google Scholar 

  91. Seyedi N, Xu X, Nasjletti A, Hintze TH. Coronary kinin generation mediates nitric oxide release after angiotensin receptor stimulation. Hypertension. 1995;26(1):164–70.

    Article  CAS  PubMed  Google Scholar 

  92. Schiffrin EL, Park JB, Intengan HD, Touyz RM. Correction of arterial structure and endothelial dysfunction in human essential hypertension by the angiotensin receptor antagonist losartan. Circulation. 2000;101(14):1653–9.

    Article  CAS  PubMed  Google Scholar 

  93. Blood Pressure Lowering Treatment Trialists’ Collaboration, Turnbull F, Neal B, et al. Blood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system. J Hypertens. 2007;25(5):951–8.

    Article  CAS  Google Scholar 

  94. Taddei S, Virdis A, Ghiadoni L, Uleri S, Magagna A, Salvetti A. Lacidipine restores endothelium-dependent vasodilation in essential hypertensive patients. Hypertension. 1997;30(6):1606–12.

    Article  CAS  PubMed  Google Scholar 

  95. Sudano I, Virdis A, Taddei S, et al. Chronic treatment with long-acting Nifedipine reduces vasoconstriction to Endothelin-1 in essential hypertension. Hypertension. 2007;49(2):285–90.

    Article  CAS  PubMed  Google Scholar 

  96. Lyons D, Webster J, Benjamin N. The effect of antihypertensive therapy on responsiveness to local intra-arterial NG-monomethyl-L-arginine in patients with essential hypertension. J Hypertens. 1994;12(9):1047–52.

    Article  CAS  PubMed  Google Scholar 

  97. Himmel HM, Whorton AR, Strauss HC. Intracellular calcium, currents, and stimulus-response coupling in endothelial cells. Hypertension. 1993;21(1):112–27.

    Article  CAS  PubMed  Google Scholar 

  98. Lupo E, Locher R, Weisser B, Vetter W. In vitro antioxidant activity of calcium antagonists against LDL oxidation compared with alpha-tocopherol. Biochem Biophys Res Commun. 1994;203(3):1803–8.

    Article  CAS  PubMed  Google Scholar 

  99. Mak IT, Boehme P, Weglicki WB. Antioxidant effects of calcium channel blockers against free radical injury in endothelial cells. Correlation of protection with preservation of glutathione levels. Circ Res. 1992;70(6):1099–103.

    Article  CAS  PubMed  Google Scholar 

  100. Morgan T, Lauri J, Bertram D, Anderson A. Effect of different antihypertensive drug classes on central aortic pressure. Am J Hypertens. 2004;17(2):118–23.

    Article  CAS  PubMed  Google Scholar 

  101. Jiang X-J, O'Rourke MF, Zhang Y-Q, He X-Y, Liu L-S. Superior effect of an angiotensin-converting enzyme inhibitor over a diuretic for reducing aortic systolic pressure. J Hypertens. 2007;25(5):1095–9.

    Article  CAS  PubMed  Google Scholar 

  102. Ohta Y, Ishizuka A, Hayashi S, et al. Effects of a selective aldosterone blocker and thiazide-type diuretic on blood pressure and organ damage in hypertensive patients. Clin Exp Hypertens. 2015;37(7):569–73.

    Article  CAS  PubMed  Google Scholar 

  103. Matsui Y, Eguchi K, O'Rourke MF, Ishikawa J, Shimada K, Kario K. Association between aldosterone induced by antihypertensive medication and arterial stiffness reduction: the J-CORE study. Atherosclerosis. 2011;215(1):184–8.

    Article  CAS  PubMed  Google Scholar 

  104. Joannides R, Bellien J, Thurlure C, Iacob M, Abeel M, Thuillez C. Fixed combination of perindopril and Indapamide at low dose improves endothelial function in essential hypertensive patients after acute administration. Am J Hypertens. 2008;21(6):679–84.

    Article  CAS  PubMed  Google Scholar 

  105. Chrysant SG. Pharmacokinetic, pharmacodynamic, and antihypertensive effects of the neprilysin inhibitor LCZ-696: sacubitril/valsartan. J Am Soc Hypertens. 2017;11:461.

    Article  CAS  PubMed  Google Scholar 

  106. Zhou M-S, Schulman IH, Jaimes EA, Raij L. Thiazide diuretics, endothelial function, and vascular oxidative stress. J Hypertens. 2008;26(3):494–500.

    Article  CAS  PubMed  Google Scholar 

  107. Muiesan ML, Salvetti M, Monteduro C, et al. Effect of treatment on flow-dependent vasodilation of the brachial artery in essential hypertension. Hypertension. 1999;33(1 Pt 2):575–80.

    Article  CAS  PubMed  Google Scholar 

  108. Muiesan ML, Salvetti M, Belotti E, et al. Effects of barnidipine in comparison with hydrochlorothiazide on endothelial function, as assessed by flow mediated vasodilatation in hypertensive patients. Blood Press. 2011;20(4):244–51.

    Article  CAS  PubMed  Google Scholar 

  109. Vergely C, Walker MK, Zeller M, et al. Antioxidant properties of indapamide, 5-OH indapamide and hydrochlorothiazide evaluated by oxygen-radical absorbing capacity and electron paramagnetic resonance. Mol Cell Biochem. 1998;178(1–2):151–5.

    Article  CAS  PubMed  Google Scholar 

  110. Calder JA, Schachter M, Sever PS. Vasorelaxant actions of 5-OH-indapamide, a major metabolite of indapamide: comparison with indapamide, hydrochlorothiazide and cicletanine. Eur J Pharmacol. 1994;256(2):185–91.

    Article  CAS  PubMed  Google Scholar 

  111. Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358(18):1887–98.

    Article  CAS  PubMed  Google Scholar 

  112. Burnier M, Narkiewicz K, Kjeldsen SE. Prevention of heart failure mortality and hospitalizations in SPRINT, EMPA-REG, ALLHAT and HYVET: are diuretics the clue? Blood Press. 2017;26(4):193–4.

    Article  PubMed  Google Scholar 

  113. Waddingham MT, Paulus WJ. Microvascular paradigm in heart failure with preserved ejection fraction: a quest for proof of concept. Circ Heart Fail. 2017;10(6):e004179.

    Article  PubMed  Google Scholar 

  114. Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013;62(4):263–71.

    Article  PubMed  Google Scholar 

  115. Mohammed SF, Hussain S, Mirzoyev SA, Edwards WD, Maleszewski JJ, Redfield MM. Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction. Circulation. 2015;131(6):550–9.

    Article  PubMed  Google Scholar 

  116. Hwang S-J, Melenovsky V, Borlaug BA. Implications of coronary artery disease in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2014;63(25 Pt A):2817–27.

    Article  PubMed  Google Scholar 

  117. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.

    Article  CAS  PubMed  Google Scholar 

  118. Schiffrin EL. Effects of aldosterone on the vasculature. Hypertension. 2006;47(3):312–8.

    Article  CAS  PubMed  Google Scholar 

  119. Williams GH. Cardiovascular benefits of aldosterone receptor antagonists: what about potassium? Hypertension. 2005;46(2):265–6.

    Article  CAS  PubMed  Google Scholar 

  120. de Souza F, Muxfeldt E, Fiszman R, Salles G. Efficacy of spironolactone therapy in patients with true resistant hypertension. Hypertension. 2010;55(1):147–52.

    Article  CAS  PubMed  Google Scholar 

  121. Yamanari H, Nakamura K, Miura D, Yamanari S, Ohe T. Spironolactone and chlorthalidone in uncontrolled elderly hypertensive patients treated with calcium antagonists and angiotensin II receptor-blocker: effects on endothelial function, inflammation, and oxidative stress. Clin Exp Hypertens. 2009;31(7):585–94.

    Article  CAS  PubMed  Google Scholar 

  122. Joffe HV, Kwong RY, Gerhard-Herman MD, Rice C, Feldman K, Adler GK. Beneficial effects of eplerenone versus hydrochlorothiazide on coronary circulatory function in patients with diabetes mellitus. J Clin Endocrinol Metab. 2007;92(7):2552–8.

    Article  CAS  PubMed  Google Scholar 

  123. Bärfacker L, Kuhl A, Hillisch A, et al. Discovery of BAY 94-8862: a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases. ChemMedChem. 2012;7(8):1385–403.

    Article  CAS  PubMed  Google Scholar 

  124. Williams B, MacDonald TM, Morant S, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;386(10008):2059–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Cockcroft JR, Chowienczyk PJ, Brett SE, et al. Nebivolol vasodilates human forearm vasculature: evidence for an L-arginine/NO-dependent mechanism. J Pharmacol Exp Ther. 1995;274(3):1067–71.

    CAS  PubMed  Google Scholar 

  126. Kubli S, Feihl F, Waeber B. Beta-blockade with nebivolol enhances the acetylcholine-induced cutaneous vasodilation. Clin Pharmacol Ther. 2001;69(4):238–44.

    Article  CAS  PubMed  Google Scholar 

  127. Dhakam Z, Yasmin MECM, et al. A comparison of atenolol and nebivolol in isolated systolic hypertension. J Hypertens. 2008;26(2):351–6.

    Article  CAS  PubMed  Google Scholar 

  128. Kampus P, Serg M, Kals J, et al. Differential effects of nebivolol and metoprolol on central aortic pressure and left ventricular wall thickness. Hypertension. 2011;57(6):1122–8.

    Article  CAS  PubMed  Google Scholar 

  129. Primatesta P, Falaschetti E, Gupta S, Marmot MG, Poulter NR. Association between smoking and blood pressure: evidence from the health survey for England. Hypertension. 2001;37(2):187–93.

    Article  CAS  PubMed  Google Scholar 

  130. Tuomilehto J, Elo J, Nissinen A. Smoking among patients with malignant hypertension. Br Med J (Clin Res Ed). 1982;284(6322):1086.

    Article  CAS  Google Scholar 

  131. Virdis A, Giannarelli C, Fritsch Neves M, Taddei S, Ghiadoni L. Cigarette Smoking and Hypertension. Curr Pharm Des. 2010;16(23):2518–25.

    Article  CAS  PubMed  Google Scholar 

  132. Messner B, Bernhard D. Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol. 2014;34(3):509–15.

    Article  CAS  PubMed  Google Scholar 

  133. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340(8828):1111–5.

    Article  CAS  PubMed  Google Scholar 

  134. Kannel WB. Importance of hypertension as a risk factor in cardiovascular disease. In: Hypertension: pathopsychology and treatment. New York, NY: McGraw-Hill; 1977. p. 888–910.

    Google Scholar 

  135. Williams B, Poulter NR, Brown MJ, et al. British hypertension society guidelines for hypertension management 2004 (BHS-IV): summary. BMJ. 2004;328(7440):634–40.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Santos-Parker JR, LaRocca TJ, Seals DR. Aerobic exercise and other healthy lifestyle factors that influence vascular aging. Adv Physiol Educ. 2014;38(4):296–307.

    Article  PubMed  PubMed Central  Google Scholar 

  137. DeSouza CA, Shapiro LF, Clevenger CM, et al. Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men. Circulation. 2000;102(12):1351–7.

    Article  CAS  PubMed  Google Scholar 

  138. Taddei S, Galetta F, Virdis A, et al. Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes. Circulation. 2000;101(25):2896–901.

    Article  CAS  PubMed  Google Scholar 

  139. McCall DO, McGartland CP, McKinley MC, et al. Dietary intake of fruits and vegetables improves microvascular function in hypertensive subjects in a dose-dependent manner. Circulation. 2009;119(16):2153–60.

    Article  CAS  PubMed  Google Scholar 

  140. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH collaborative research group. N Engl J Med. 1997;336(16):1117–24.

    Article  CAS  PubMed  Google Scholar 

  141. Anter E, Thomas SR, Schulz E, Shapira OM, Vita JA, Keaney JF. Activation of endothelial nitric-oxide synthase by the p38 MAPK in response to black tea polyphenols. J Biol Chem. 2004;279(45):46637–43.

    Article  CAS  PubMed  Google Scholar 

  142. Widlansky ME, Duffy SJ, Hamburg NM, et al. Effects of black tea consumption on plasma catechins and markers of oxidative stress and inflammation in patients with coronary artery disease. Free Radic Biol Med. 2005;38(4):499–506.

    Article  CAS  PubMed  Google Scholar 

  143. Appel LJ, Brands MW, Daniels SR, et al. Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension. 2006;47(2):296–308.

    Article  CAS  PubMed  Google Scholar 

  144. He FJ, MacGregor GA. Effect of modest salt reduction on blood pressure: a meta-analysis of randomized trials. Implications for public health. J Hum Hypertens. 2002;16(11):761–70.

    Article  CAS  PubMed  Google Scholar 

  145. The Trials of Hypertension Prevention Collaborative Research Group. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The trials of hypertension prevention, phase II. Arch Intern Med. 1997;157(6):657–67.

    Article  Google Scholar 

  146. Langford HG, Blaufox MD, Oberman A, et al. Dietary therapy slows the return of hypertension after stopping prolonged medication. JAMA. 1985;253(5):657–64.

    Article  CAS  PubMed  Google Scholar 

  147. Whelton PK, Appel LJ, Espeland MA, et al. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). TONE collaborative research group. JAMA. 1998;279(11):839–46.

    Article  CAS  PubMed  Google Scholar 

  148. Weir MR, Hall PS, Behrens MT, Flack JM. Salt and blood pressure responses to calcium antagonism in hypertensive patients. Hypertension. 1997;30(3 Pt 1):422–7.

    Article  CAS  PubMed  Google Scholar 

  149. Appel LJ, Espeland MA, Easter L, Wilson AC, Folmar S, Lacy CR. Effects of reduced sodium intake on hypertension control in older individuals: results from the trial of nonpharmacologic interventions in the elderly (TONE). Arch Intern Med. 2001;161(5):685–93.

    Article  CAS  PubMed  Google Scholar 

  150. Kopkan L, Majid DSA. Superoxide contributes to development of salt sensitivity and hypertension induced by nitric oxide deficiency. Hypertension. 2005;46(4):1026–31.

    Article  CAS  PubMed  Google Scholar 

  151. Majid DSA, Kopkan L. Nitric oxide and superoxide interactions in the kidney and their implication in the development of salt-sensitive hypertension. Clin Exp Pharmacol Physiol. 2007;34(9):946–52.

    Article  CAS  PubMed  Google Scholar 

  152. Kopkan L, Castillo A, Navar LG, Majid DSA. Enhanced superoxide generation modulates renal function in ANG II-induced hypertensive rats. Am J Physiol Renal Physiol. 2006;290(1):F80–6.

    Article  CAS  PubMed  Google Scholar 

  153. Gates PE, Tanaka H, Hiatt WR, Seals DR. Dietary sodium restriction rapidly improves large elastic artery compliance in older adults with systolic hypertension. Hypertension. 2004;44(1):35–41.

    Article  CAS  PubMed  Google Scholar 

  154. Cogswell ME, Mugavero K, Bowman BA, Frieden TR. Dietary sodium and cardiovascular disease risk--measurement matters. N Engl J Med. 2016;375(6):580–6.

    Article  PubMed  PubMed Central  Google Scholar 

  155. O'Donnell M, Mente A, Yusuf S. Sodium and cardiovascular disease. N Engl J Med. 2014;371(22):2137–8.

    PubMed  Google Scholar 

  156. Mozaffarian D, Fahimi S, Singh GM, et al. Global sodium consumption and death from cardiovascular causes. N Engl J Med. 2014;371(7):624–34.

    Article  PubMed  Google Scholar 

  157. Mancia G, Oparil S, Whelton PK, et al. The technical report on sodium intake and cardiovascular disease in low- and middle-income countries by the joint working group of the world heart federation, the European Society of Hypertension and the European public health association. Eur Heart J. 2017;38(10):712–9.

    PubMed  Google Scholar 

  158. Xin X, He J, Frontini MG, Ogden LG, Motsamai OI, Whelton PK. Effects of alcohol reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2001;38(5):1112–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Reserach Centre, University of Glasgow, Glasgow, UK

    Alan C. Cameron, Giacomo Rossitto, Ninian N. Lang & Rhian M. Touyz

Authors
  1. Alan C. Cameron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giacomo Rossitto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ninian N. Lang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rhian M. Touyz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rhian M. Touyz .

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

Cameron, A.C., Rossitto, G., Lang, N.N., Touyz, R.M. (2019). Antihypertensive Drugs and Vascular Health. 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_37

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-75310-2_37

  • 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