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Vascular Effects of Antihypertensive Drug Therapy

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Abstract

Hypertension is associated with structural and functional alterations in the vasculature that lead to hemodynamic disturbances and target organ damage. The benefit of reducing blood pressure on risk reduction is well established. Antihypertensive drugs partially correct hypertensive vascular changes by a number of mechanisms, but their influence may vary in different vascular beds. Recently, combinations of drugs with complementary or synergistic effects have shown favorable effects on the vasculature; these combinations may contribute to risk reduction and improve outcomes in the future. Clinical trial evidence has shown an improvement in morbidity and mortality indicators that could be related to vascular effects of antihypertensive drugs, but this effect needs to be proven in future long-term prospective studies involving simultaneous evaluation of small-artery and large-artery properties.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Schiffrin EL: Effects of antihypertensive drugs on vascular remodeling: Do they predict outcome in response to antihypertensive therapy? Curr Opin Nephrol Hypertens 2001, 10:617–624.

    Article  CAS  PubMed  Google Scholar 

  2. Gradman AH: Role of angiotensin II type 1 receptor antagonists in the treatment of hypertension in patients aged >or=65 years. Drugs Aging 2009, 26:751–767.

    Article  CAS  PubMed  Google Scholar 

  3. Law MR, Morris JK, Wald NJ: Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. Br Med J 2009, 338:b1665.

    Article  CAS  Google Scholar 

  4. • London GM: Brachial arterial pressure to assess cardiovascular structural damage: an overview and lessons from clinical trials. J Nephrol 2008, 21:23–31. This overview mechanistically describes the impact of vascular changes of small and large arteries on cardiovascular risk.

    PubMed  Google Scholar 

  5. • Safar ME, Jankowski P: Central blood pressure and hypertension: role in cardiovascular risk assessment. Clin Sci 2009, 116:273–282. This review focuses on the role in cardiovascular risk of hemodynamic changes associated with vascular remodeling.

    Article  PubMed  Google Scholar 

  6. Asmar RG, London GM, O’Rourke ME, Safar ME: Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: a comparison with atenolol. Hypertension 2001, 38:922–926.

    Article  CAS  PubMed  Google Scholar 

  7. Williams B, Lacy PS, Thom SM, et al.: Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation 2006, 113:1213–1225.

    Article  CAS  PubMed  Google Scholar 

  8. •• Agabiti-Rosei E, Heagerty AM, Rizzoni D: Effects of antihypertensive treatment on small artery remodelling. J Hypertens 2009, 27:1107–1114. This is an excellent review of recent evidence on vascular effects of antihypertensive drugs and the prognostic significance of small-artery remodeling.

    Article  CAS  PubMed  Google Scholar 

  9. • Levy B, Schiffrin EL, Mourad JJ, et al.: Impaired tissue perfusion: a pathology common to hypertension, obesity and diabetes. Circulation 2008, 118:968–976. This is a review of mechanisms whereby vascular remodeling results in impaired tissue perfusion, which is a common pathophysiologic feature of hypertension, obesity, and diabetes.

    Article  PubMed  Google Scholar 

  10. Schiffrin EL: Reactivity of small blood vessels in hypertension: relation with structural changes. Hypertension 1992, 19(2 Suppl):II1–II9.

    CAS  PubMed  Google Scholar 

  11. Schiffrin EL: Remodeling of resistance arteries in essential hypertension and effects of antihypertensive treatment. Am J Hypertens 2004, 17:1192–1200.

    Article  CAS  PubMed  Google Scholar 

  12. Riccioni G: The effect of antihypertensive drugs on carotid intima media thickness: an up-to-date review. Curr Med Chem 2009, 16:988–996.

    Article  CAS  PubMed  Google Scholar 

  13. Schiffrin EL, Touyz RM: Medical Editorial: From bedside to bench to bedside: Role of renin-angiotensin-aldosterone system in remodeling of resistance arteries in hypertension. Am J Physiol Heart Circ Physiol 2004, 287:H435–H446.

    Article  CAS  PubMed  Google Scholar 

  14. Park JB, Schiffrin EL: Small artery remodeling is the most prevalent (earliest?) form of target organ damage in mild essential hypertension. J Hypertens 2001, 19:921–930.

    Article  CAS  PubMed  Google Scholar 

  15. Rizzoni D, Porteri E, Boari GE, et al.: Prognostic significance of small-artery structure in hypertension. Circulation 2003, 108:2230–2235.

    Article  PubMed  Google Scholar 

  16. • Heagerty AM: Predicting hypertension complications from small artery structure. J Hypertens 2007, 25:939–940. This article provides useful evidence on the prognostic significance of small-artery remodeling and hypertensive complications.

    Article  CAS  PubMed  Google Scholar 

  17. Rizzoni D, Palombo C, Porteri E, et al.: Relationships between coronary flow vasodilator capacity and small artery remodelling in hypertensive patients. J Hypertens 2003, 21:625–631.

    Article  CAS  PubMed  Google Scholar 

  18. • Schiffrin EL: The vascular phenotypes in hypertension: relation to the natural history of hypertension. J Am Soc Hypertens 2007, 1:56–67. This article discusses the evolution of different subsets of hypertensive subjects and the role that vascular remodeling plays in this evolution. It also raises the possibility of cross-talk between large and small vessels.

    Article  PubMed  Google Scholar 

  19. Ghiadoni L, Bruno RM, Stea F, et al.: Central blood pressure, arterial stiffness, and wave reflection: new targets of treatment in essential hypertension. Curr Hypertens Rep 2009, 11:190–196.

    Article  PubMed  Google Scholar 

  20. • Mathiassen ON, Buus NH, Larsen ML, et al.: Small artery structure adapts to vasodilatation rather than to blood pressure during antihypertensive treatment. J Hypertens 2007, 25:1027–1034. This study directly shows for the first time the role of drug-induced vasodilatation in correcting vascular alterations in hypertension.

    Article  CAS  PubMed  Google Scholar 

  21. Touyz RM, Schiffrin EL: Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacol Rev 2000, 52:639–672.

    CAS  PubMed  Google Scholar 

  22. Ferrari R, Fox K: Insight into the mode of action of ACE inhibition in coronary artery disease: the ultimate ‘EUROPA’ story. Drugs 2009, 69:265–277.

    Article  CAS  PubMed  Google Scholar 

  23. 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, 101:1653–1659.

    CAS  PubMed  Google Scholar 

  24. Ghiadoni L, Virdis A, Magagna A, et al.: Effect of the angiotensin II type 1 receptor blocker candesartan on endothelial function in patients with essential hypertension. Hypertension 2000, 35:501–506.

    CAS  PubMed  Google Scholar 

  25. • Battegay EJ, de Miguel LS, Petrimpol M, Humar R: Effects of anti-hypertensive drugs on vessel rarefaction. Curr Opin Pharmacol 2007, 7:151–157. The paper discusses the likely role of bradykinin-induced angiogenesis during RAAS inhibition in correcting vascular rarefaction and preventing target organ damage in hypertension.

    Article  CAS  PubMed  Google Scholar 

  26. Rizos CV, Elisaf MS, Liberopoulos EN: Are the pleiotropic effects of telmisartan clinically relevant? Curr Pharm Des 2009, 15:2815–2832.

    Article  CAS  PubMed  Google Scholar 

  27. Umemoto S, Tanaka M, Kawahara S, et al.: Calcium antagonist reduces oxidative stress by upregulating Cu/Zn superoxide dismutase in stroke-prone spontaneously hypertensive rats. Hypertens Res 2004, 27:877–885.

    Article  CAS  PubMed  Google Scholar 

  28. • Koh KK, Quon MJ, Lee SJ, et al.: Efonidipine simultaneously improves blood pressure, endothelial function, and metabolic parameters in nondiabetic patients with hypertension. Diabetes Care 2007, 30:1605–1607. This study shows the beneficial effects of CCBs in improving vascular abnormalities and the metabolic profile in hypertensive patients.

    Article  CAS  PubMed  Google Scholar 

  29. Maffei A, Lembo G: Nitric oxide mechanisms of nebivolol. Ther Adv Cardiovasc Dis 2009, 3:317–327.

    Article  PubMed  Google Scholar 

  30. Agabiti Rosei E, Rizzoni D: Metabolic profile of nebivolol, a beta-adrenoceptor antagonist with unique characteristics. Drugs 2007, 67:1097–1107.

    Article  PubMed  Google Scholar 

  31. Galderisi M, D’Errico A: Beta-blockers and coronary flow reserve: the importance of a vasodilatory action. Drugs 2008, 68:579–590.

    Article  CAS  PubMed  Google Scholar 

  32. Lacolley P, Labat C, Pujol A, et al.: Increased carotid wall elastic modulus and fibronectin in aldosterone-salt-treated rats: effects of eplerenone. Circulation 2002, 106:2848–2853.

    Article  CAS  PubMed  Google Scholar 

  33. •• Savoia C, Touyz RM, Amiri F, Schiffrin EL: Selective mineralocorticoid receptor blocker eplerenone reduces resistance artery stiffness in hypertensive patients. Hypertension 2008, 51:432–439. This is the only study showing the vascular effects of a mineralocorticoid receptor antagonist on small-artery properties in humans.

    Article  CAS  PubMed  Google Scholar 

  34. Sudano I, Hermann M, Ruschitzka FT: Endothelin-receptor antagonists in arterial hypertension: further indications? Curr Hypertens Rep 2007, 9:59–65.

    Article  CAS  PubMed  Google Scholar 

  35. Weber MA, Black H, Bakris G, et al: A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomised, double-blind, placebo-controlled trial. Lancet 2009, 374:1423–1431.

    Article  CAS  PubMed  Google Scholar 

  36. Khanna A, Lefkowitz L, White WB: Evaluation of recent fixed-dose combination therapies in the management of hypertension. Curr Opin Nephrol Hypertens 2008, 17:477–483.

    Article  CAS  PubMed  Google Scholar 

  37. Ghiadoni L, Magagna A, Versari D, et al.: Different effect of antihypertensive drugs on conduit artery endothelial function. Hypertension 2003, 41:1281–1286.

    Article  CAS  PubMed  Google Scholar 

  38. 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, 23:551–556.

    Article  CAS  PubMed  Google Scholar 

  39. Mitchell GF, Lacourciere Y, Arnold JM, et al.: Changes in aortic stiffness and augmentation index after acute converting enzyme or vasopeptidase inhibition. Hypertension 2005, 46:1111–1117.

    Article  CAS  PubMed  Google Scholar 

  40. Ichihara A, Kaneshiro Y, Takemitsu T, Sakoda M: Effects of amlodipine and valsartan on vascular damage and ambulatory blood pressure in untreated hypertensive patients. J Hum Hypertens 2006, 20:787–794.

    Article  CAS  PubMed  Google Scholar 

  41. McEniery CM, Schmitt M, Qasem A, et al.: Nebivolol increases arterial distensibility in vivo. Hypertension 2004, 44:305–310.

    Article  CAS  PubMed  Google Scholar 

  42. Lekakis JP, Protogerou A, Papamichael C, et al.: Effect of nebivolol and atenolol on brachial artery flow-mediated vasodilation in patients with coronary artery disease. Cardiovasc Drugs Ther 2005, 19:277–281.

    Article  CAS  PubMed  Google Scholar 

  43. Kaiser T, Heise T, Nosek L, et al.: Influence of nebivolol and enalapril on metabolic parameters and arterial stiffness in hypertensive type 2 diabetic patients. J Hypertens 2006, 24:1397–1403.

    Article  CAS  PubMed  Google Scholar 

  44. •• Kakou A, Bezie Y, Mercier N, et al.: Selective reduction of central pulse pressure under angiotensin blockage in SHR: role of the fibronectin-alpha5beta1 integrin complex. Am J Hypertens 2009, 22:711–717. This interesting study reports the experimental evidence on the mechanisms responsible for the beneficial effects of RAAS inhibitors on central hemodynamics.

    Article  CAS  PubMed  Google Scholar 

  45. Buus NH, Jorgensen CG, Mulvany MJ, Sorensen KE: Large and small artery endothelial function in patients with essential hypertension—effect of ACE inhibition and beta-blockade. Blood Press 2007, 16:106–113.

    Article  CAS  PubMed  Google Scholar 

  46. Bellido CA, Iavicoli OR, Rusak EJ, et al.: Continuous improvement of arterial compliance beyond blood pressure decrease after 5 years of antihypertensive treatment. J Clin Hypertens (Greenwich) 2006, 8:555–560.

    Article  Google Scholar 

  47. • Kosch M, Levers A, Lang D, et al.: A randomized, double-blind study of valsartan versus metoprolol on arterial distensibility and endothelial function in essential hypertension. Nephrol Dial Transplant 2008, 23:2280–2285. This study shows similar short-term effects of β-blockade and angiotensin blockade on large-artery properties.

    Article  CAS  PubMed  Google Scholar 

  48. Song H, Bao W, Wang H, et al.: Effects of extended-release felodipine on endothelial vasoactive substances in patients with essential hypertension. Clin Chem Lab Med 2008, 46:393–395.

    Article  CAS  PubMed  Google Scholar 

  49. • Ghiadoni L, Magagna A, Kardasz I, et al.: Fixed dose combination of perindopril and indapamide improves peripheral vascular function in essential hypertensive patients. Am J Hypertens 2009, 22:506–512. This study showed pressure-independent effects of the treatment combination on endothelial function in hypertensive patients.

    Article  CAS  PubMed  Google Scholar 

  50. Schwartzkopff B, Brehm M, Mundhenke M, Strauer BE: Repair of coronary arterioles after treatment with perindopril in hypertensive heart disease. Hypertension 2000, 36:220–225.

    CAS  PubMed  Google Scholar 

  51. 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, 25:699–703.

    CAS  PubMed  Google Scholar 

  52. 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.

    CAS  PubMed  Google Scholar 

  53. Schiffrin EL, Deng LY, Larochelle P: Progressive improvement in the structure of resistance arteries of hypertensive patients after 2 years of treatment with an angiotensin I-converting enzyme inhibitor. Comparison with effects of a beta-blocker. Am J Hypertens 1995, 8:229–236.

    Article  CAS  PubMed  Google Scholar 

  54. Schiffrin EL, Park JB, Pu Q: Effect of crossing over hypertensive patients from a beta-blocker to an angiotensin receptor antagonist on resistance artery structure and on endothelial function. J Hypertens 2002, 20:71–78.

    Article  CAS  PubMed  Google Scholar 

  55. Rizzoni D, Porteri E, De Ciuceis C, et al.: Effect of treatment with candesartan or enalapril on subcutaneous small artery structure in hypertensive patients with noninsulin-dependent diabetes mellitus. Hypertension 2005, 45:659–665.

    Article  CAS  PubMed  Google Scholar 

  56. Savoia C, Touyz RM, Endemann DH, et al.: Angiotensin receptor blocker added to previous antihypertensive agents on arteries of diabetic hypertensive patients. Hypertension 2006, 48:271–277.

    Article  CAS  PubMed  Google Scholar 

  57. Schiffrin EL, Deng LY: Structure and function of resistance arteries of hypertensive patients treated with a β-blocker or a calcium channel antagonist. J Hypertens 1996, 14:1247–1255.

    Article  CAS  PubMed  Google Scholar 

  58. Schiffrin EL, Pu Q, Park JB: Effect of amlodipine compared to atenolol on small arteries of previously untreated essential hypertensive patients. Am J Hypertens 2002, 15:105–110.

    Article  CAS  PubMed  Google Scholar 

  59. Intengan HD, Schiffrin EL: Disparate effects of carvedilol versus metoprolol treatment of stroke-prone spontaneously hypertensive rats on endothelial function of resistance arteries. J Cardiovasc Pharmacol 2000, 35:763–768.

    Article  CAS  PubMed  Google Scholar 

  60. • Savoia C, Touyz RM, Volpe M, Schiffrin EL: Angiotensin type 2 receptor in resistance arteries of type 2 diabetic hypertensive patients. Hypertension 2007, 49:341–346. This study shows upregulation of AT 2 receptors in hypertensive diabetic individuals treated with an ARB, and the role of AT 2 receptors in the beneficial effects of type 1 receptor blockade on endothelial function in humans.

    Article  CAS  PubMed  Google Scholar 

  61. • Inaba S, Iwai M, Tomono Y, et al.: Prevention of vascular injury by combination of an AT1 receptor blocker, olmesartan, with various calcium antagonists. Am J Hypertens 2009, 22:145–150. This detailed study shows the beneficial effects on various pathways involved in vascular injury of combining an ARB with various calcium antagonists.

    Article  CAS  PubMed  Google Scholar 

  62. Versari D, Virdis A, Ghiadoni L, et al.: Effect of verapamil, trandolapril and their combination on vascular function and structure in essential hypertensive patients. Atherosclerosis 2009, 205:214–220.

    Article  CAS  PubMed  Google Scholar 

  63. Yamamoto E, Kataoka K, Dong YF, et al.: Aliskiren enhances the protective effects of valsartan against cardiovascular and renal injury in endothelial nitric oxide synthase-deficient mice. Hypertension 2009, 54:633–638.

    Article  CAS  PubMed  Google Scholar 

  64. Cicero AF, Veronesi M, Prandin MG, et al.: Effects of AT1 receptor and beta1 receptor blocking on blood pressure, peripheral hemodynamic and lipid profile in statin-treated hypertensive hypercholesterolemic patients. Fundam Clin Pharmacol 2009, 23:583–588.

    Article  CAS  PubMed  Google Scholar 

  65. Diep QN, El Mabrouk M, Cohn JS, et al.: Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats: role of peroxisome proliferator-activated receptor-gamma. Circulation 2002, 105:2296–2302.

    Article  CAS  PubMed  Google Scholar 

  66. Leibovitz E, Schiffrin EL: PPAR activation: a new target for the treatment of hypertension. Invited review. J Cardiovasc Pharmacol 2007, 50:120–125.

    Article  CAS  Google Scholar 

  67. Nakamura T, Yamamoto E, Kataoka K, et al.: Beneficial effects of pioglitazone on hypertensive cardiovascular injury are enhanced by combination with candesartan. Hypertension 2008, 51:296–301.

    Article  CAS  PubMed  Google Scholar 

  68. • Savoia C, Ebrahimian T, Lemarié CA, et al.: Countervailing vascular effects of rosiglitazone in high cardiovascular risk mice: role of oxidative stress and PRMT-1. Clin Sci 2010, 118:583–592. This study demonstrates that in mice with high cardiovascular risk, rosiglitazone improves some aspects of the vasculature (remodeling of vessels) but worsens endothelial function via increased synthesis of asymmetric dimethyl arginine (ADMA). This effect may be related to the adverse cardiovascular profile recently suggested for this glitazone in advanced diabetes in humans.

    CAS  PubMed  Google Scholar 

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Acknowledgments

Work of the authors was supported by the Canadian Institutes of Health Research (CIHR) grants 37137 and 82790, a Canada Research Chair (CRC) on Hypertension and Vascular Research from the CIHR/CRC Program of the Government of Canada, and the Canada Fund for Innovation to ELS.

Disclosure

Dr. Schiffrin has received the Pfizer Cardiovascular Award; has served on the Advisory Boards of Bristol-Myers Squibb, Novartis, and Pfizer; and has been a speaker for Bristol-Myers Squibb and Daiichi Sankyo.

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  1. Lady Davis Institute, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Côte-Ste-Catherine Road, Montreal, Quebec, Canada, H3T 1E2

    Asia Rehman

  2. Lady Davis Institute and Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, #B-127, 3755 Côte-Ste-Catherine Road, Montreal, Quebec, Canada, H3T 1E2

    Ernesto L. Schiffrin

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Correspondence to Ernesto L. Schiffrin.

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Rehman, A., Schiffrin, E.L. Vascular Effects of Antihypertensive Drug Therapy. Curr Hypertens Rep 12, 226–232 (2010). https://doi.org/10.1007/s11906-010-0117-3

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