Skip to main content
Log in

Effects of antihypertensive therapy on hypertensive vascular disease

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Hypertension is associated with alterations in the structure, function, and mechanical properties of large and small arteries. Changes in the endothelium, smooth muscle cell, extracellular matrix, and possibly the adventitia, contribute to complications of hypertension. In large arteries, vascular hypertrophy is found, often with increased stiffness of media components. In small arteries, particularly in mild hypertension, rearrangement of smooth muscle cells around a smaller lumen without changes in media volume (eutrophic remodeling) occurs; in more severe hypertension, hypertrophic remodeling with increased vascular stiffness can be found. Vascular remodeling is accompanied by an increase in the extracellular matrix, particularly collagen deposition. Recent studies have demonstrated that vascular remodeling and endothelial dysfunction of small and large vessels may be normalized by treatment with some antihypertensive agents (angiotensin converting enzyme inhibitors, angiotensin AT1 receptor antagonists, and long-acting calcium channel blockers). Angiotensin converting enzyme inhibitors have now been shown to improve outcomes in hypertensive patients, an effect that may in part be related to the vascular protective effects reviewed here.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Folkow B: Physiological aspects of primary hypertension. Physiol Rev 1982, 62:347–504.

    PubMed  CAS  Google Scholar 

  2. Mulvany MJ, Aalkjaer C: Structure and function of small arteries. Physiol Rev 1990, 70:921–971.

    PubMed  CAS  Google Scholar 

  3. Schiffrin EL: Reactivity of small blood vessels in hypertension. Relationship with structural changes. Hypertension 1992, 19(suppl II):II1-II9.

    PubMed  CAS  Google Scholar 

  4. Heagerty AM, Aalkjaer C, Bund SJ, et al.: Small artery structure in hypertension: dual processes of remodelling and growth. Hypertension 1993, 21:391–397.

    PubMed  CAS  Google Scholar 

  5. Fang J, Madhavan S, Cohen H, et al.: Measures of blood pressure and myocardial infarction in treated hypertensive patients. J Hypertens 1995, 13:413–419.

    PubMed  CAS  Google Scholar 

  6. Benetos A, Rudnichi A, Safar M, et al.: Pulse pressure and cardiovascular mortality in normotensive and hypertensive subjects. Hypertension 1998, 32:560–564. This study underlines the importance of pulse pressure as a cardiovascular risk factor in hypertensive patients.

    PubMed  CAS  Google Scholar 

  7. Hayoz D, Rutschmann B, Perret F, et al.: Conduit artery compliance and distensibility are not necessarily reduced in hypertension. Hypertension 1992, 20:1–6.

    PubMed  CAS  Google Scholar 

  8. Christensen KL, Mulvany MJ: Mesenteric arcade arteries contribute substantially to vascular resistance in conscious rats. J Vasc Res 1993, 30:73–79.

    PubMed  CAS  Google Scholar 

  9. Folkow B: Hypertensive structural changes in systemic precapillary resistance vessels: how important are they for in vivo haemodynamics? J Hypertens 1995, 13:1546–1559.

    PubMed  CAS  Google Scholar 

  10. Izzard AS, Heagerty AM: Hypertension and the vasculature: arterioles and the myogenic response. J Hypertens 1995, 13:1–4.

    PubMed  CAS  Google Scholar 

  11. Brush JE, Cannon RO, Schenke WH, et al.: Angina due to coronary microvascular disease in hypertensive patients without left ventricular hypertrophy. N Engl J Med 1988, 319:1302–1307.

    PubMed  Google Scholar 

  12. Fuster V, Badimon L, Badimon JJ, et al.: The pathogenesis of acute coronary syndromes. N Engl J Med 1992, 326:242–250, 310–318.

    PubMed  CAS  Google Scholar 

  13. Kinlay S, Selwyn AP, Libby P, et al.: Inflammation, the endothelium, and the acute coronary syndromes. J Cardiovasc Pharmacol 1998, 32:S62-S66. A useful review on inflammation of the vascular wall of coronary arteries and the pathogenesis of acute coronary syndrome.

    PubMed  CAS  Google Scholar 

  14. Hasdai D, Gibbons RJ, Holmes DR Jr, et al.: Coronary endothelial dysfunction is associated with myocardial perfusion defects. Circulation 1997, 96:3390–3395.

    PubMed  CAS  Google Scholar 

  15. Collins R, Peto F, MacMahon S, et al.: Blood pressure, stroke, and coronary heart disease, part 2: short term reductions in blood pressure: overview of randomized drug trials in their epidemiological context. Lancet 1990, 335:827–838.

    PubMed  CAS  Google Scholar 

  16. MacMahon SW, Cutler JA, Stamler J: Antihypertensive drug treatment. Potential, expected, and observed effects on stroke and on coronary heart disease. Hypertension 1989, 13(Suppl I):I45-I50.

    PubMed  CAS  Google Scholar 

  17. McDonald’s Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles, edn 4. Edited by Nichols WW, O’Rourke MF. London: E. Arnold; 1998:377–395.

    Google Scholar 

  18. Tice FD, Peterson JW, Orsinelli DA, et al.: Vascular hypertrophy is an early finding in essential hypertension and is related to arterial pressure waveform contour. Am Heart J 1996, 132:621–627.

    PubMed  CAS  Google Scholar 

  19. Roman MJ, Pickering TG, Pini R, et al.: Prevalence and determinants of cardiac and vascular hypertrophy in hypertension. Hypertension 1995, 26:369–373.

    PubMed  CAS  Google Scholar 

  20. Laurent S, Girerd X, Mourad JJ, et al.: Elastic modulus of the radial artery wall material is not increased in patients with essential hypertension. Arterioscler Thromb 1994, 14:1223–1231.

    PubMed  CAS  Google Scholar 

  21. Weber R, Stergiopulos N, Brunner HR, et al.: Contributions of vascular tone and structure to elastic properties of a medium-sized artery. Hypertension 1996, 27(Pt 2):816–822.

    PubMed  CAS  Google Scholar 

  22. Zanchi A, Wiesel P, Aubert JF, et al.: Time course changes of the mechanical properties of the carotid artery in renal hypertensive rats. Hypertension 1997, 29:1199–1203. This interesting paper showed for the first time that compliance of the carotid may be initially increased in hypertension and reduced later in the course of the disease.

    PubMed  CAS  Google Scholar 

  23. van Gorp AW, van Ingen Schenau DS, Hoeks AP, et al.: Aortic wall properties in normotensive and hypertensive rats of various ages in vivo. Hypertension 1995, 26:363–368.

    PubMed  Google Scholar 

  24. Lacolley P, Bezie Y, Girerd X, et al.: Aortic distensibility and structural changes in sinoaortic-denervated rats. Hypertension 1995, 26:337–340.

    PubMed  CAS  Google Scholar 

  25. Gariepy J, Massonneau M, Levenson J, et al.: Evidence for in vivo carotid and femoral wall thickening in human hypertension. Groupe de Prevention Cardio-vasculaire en Medecine du Travail. Hypertension 1993, 22:111–118.

    PubMed  CAS  Google Scholar 

  26. Girerd X, Giannattasio C, Moulin C, et al.: Regression of radial artery wall hypertrophy and improvement of carotid artery compliance after long-term antihypertensive treatment in elderly patients. J Am Coll Cardiol 1998, 31:1064–1073. This elegant study demonstrates that in elderly hypertensive patients, antihypertensive treatment may cause regression of changes of the carotid and radial arteries.

    PubMed  CAS  Google Scholar 

  27. Laurent S: Arterial wall hypertrophy and stiffness in essential hypertensive patients. Hypertension 1995, 26:355–362.

    PubMed  CAS  Google Scholar 

  28. Roman MJ, Saba PS, Pini R, et al.: Parallel cardiac and vascular adaptation in hypertension. Circulation 1992, 86:1909–1918.

    PubMed  CAS  Google Scholar 

  29. Levenson J, Simon A: Phase III and phase IV trials: noninvasive assessment of efficacy endpoints in vessel walls. Am J Cardiol 1998, 81:67F-68F.

    PubMed  CAS  Google Scholar 

  30. Zanchetti A, Bond MG, Hennig M, et al.: Risk factors associated with alterations in carotid intima-media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis. Hypertension 1998, 16:949–961. This important study establishes the relationships of numerous cardiovascular risk factors and vascular disease in a large cohort of hypertensive patients.

    CAS  Google Scholar 

  31. Olsen MH, Fossum E, Hjerkinn E, et al.: Relative influence of insulin resistance versus blood pressure on vascular changes in longstanding hypertension. ICARUS, a LIFE sub study. J Hypertens 2000, 18:75–81.

    PubMed  CAS  Google Scholar 

  32. Khattar RS, Senior R, Swales JD, et al.: Value of ambulatory intra-arterial blood pressure monitoring in the long term prediction of left ventricular hypertrophy and carotid atherosclerosis in essential hypertension. J Human Hypertens 1999, 13:111–116.

    CAS  Google Scholar 

  33. Mancini GBJ: Carotid intima-media thickness as a measure of vascular target organ damage. Curr Hypertens Rep 2000, 2:71–77.

    PubMed  CAS  Google Scholar 

  34. Sorlie PD, Sharrett AR, Patsch W, et al.: The relationship between lipids/lipoproteins and atherosclerosis in African Americans and whites: The Atherosclerosis Risk in Communities Study. Ann Epidemiol 1999, 9:149–158.

    PubMed  CAS  Google Scholar 

  35. Ferrières J, Elias A, Ruidavets JB, et al.: Carotid intima-media thickness and coronary heart disease risk factors in a low-risk population. Hypertension 1999, 17:743–748.

    Google Scholar 

  36. Thalhammer C, Balzuweit B, Busjahn A, et al.: Endothelial cell dysfunction and arterial wall hypertrophy are associated with disturbed carbohydrate metabolism in patients at risk for cardiovascular disease. Arterioscler Thromb Vasc Biol 1999, 19:1173–1179.

    PubMed  CAS  Google Scholar 

  37. Laurent S, Caviezel B, Beck L, et al.:Carotid artery distensibility and distending pressure in hypertensive humans. Hypertension 1994, 23(Pt 2):878–883.

    PubMed  CAS  Google Scholar 

  38. Asmar R, Benetos A, Topouchian J, et al.: Assessment of arterial distensibility by automatic pulse wave velocity measurement. Validation and clinical application studies. Hypertension 1995, 26:485–490.

    PubMed  CAS  Google Scholar 

  39. Watt TB Jr, Burrus CS: Arterial pressure contour analysis for estimating human vascular properties. J Appl Physiol 1976, 40:171–176.

    PubMed  Google Scholar 

  40. McVeigh GE, Bratteli CW, Morgan DJ, et al.: Age-related abnormalities in arterial compliance identified by pressure pulse contour analysis: aging and arterial compliance. Hypertension 1999, 33:1392–1398.

    PubMed  CAS  Google Scholar 

  41. Kelly RP, Tunin R, Kass DA: Effect of reduced aortic compliance on cardiac efficiency and contractile function of in situ canine left ventricle. Circ Res 1992, 71:490–502.

    PubMed  CAS  Google Scholar 

  42. Sytkowski PA, D’Agostino RB, Belanger AJ, et al.: Secular trends in long-term sustained hypertension, long-term treatment, and cardiovascular mortality. The Framingham Heart Study 1950 to 1990. Circulation 1996, 93:697–703.

    PubMed  CAS  Google Scholar 

  43. Boutouyrie P, Bussy C, Lacolley P, et al.: Association between local pulse pressure, mean blood pressure, and large-artery remodeling. Circulation 1999, 100:1387–1393. This important report highlights the role of local pulse pressure as a determinant of vascular remodeling.

    PubMed  CAS  Google Scholar 

  44. Baumbach G: Effects of increased pulse pressure on cerebral arterioles. Hypertens 1996, 27:159–167.

    CAS  Google Scholar 

  45. Christensen KL: Reducing pulse pressure in hypertension may normalize small artery structure. Hypertension 1991, 18:722–727.

    PubMed  CAS  Google Scholar 

  46. Schiffrin EL, Deng LY: Relationship of small artery structure with systolic, diastolic and pulse pressure in essential hypertension. J Hypertens 1999, 17:381–387.

    PubMed  CAS  Google Scholar 

  47. O’Rourke M, Frohlich ED: Pulse pressure: is this a clinically useful risk factor? Hypertension 1999, 34:372–374.

    PubMed  CAS  Google Scholar 

  48. Antony I, Lerebours G, Nitenberg A: Loss of flow-dependent coronary artery dilatation in patients with hypertension. Circulation 1995, 91:1624–1628.

    PubMed  CAS  Google Scholar 

  49. Solzbach U, Hornig B, Jeserich M, et al.: Vitamin C improves endothelial dysfunction of epicardial coronary arteries in hypertensive patients. Circulation 1997, 96:1513–1519.

    PubMed  CAS  Google Scholar 

  50. Gokce N, Keaney JF Jr, Frei B, et al.: Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 1999, 99:3234–3240. This elegant study indirectly demonstrates the role of oxidative stress in endothelial dysfunction of the coronary circulation with the use of vitamin C as an antioxidant.

    PubMed  CAS  Google Scholar 

  51. Korsgaard N, Aalkjaer C, Heagerty AM, et al.: Histology of subcutaneous small arteries from patients with essential hypertension. Hypertension 1993, 22:523–526.

    PubMed  CAS  Google Scholar 

  52. Schiffrin EL, Deng LY, Larochelle P: Morphology of resistance arteries and comparison of effects of vasoconstrictors in mild essential hypertensive patients. Clin Invest Med 1993, 16:177–186.

    PubMed  CAS  Google Scholar 

  53. Mulvany MJ, Baumbach GL, Aalkjaer C, et al.: Vascular remodeling [letter]. Hypertension 1996, 27:505–506.

    Google Scholar 

  54. Intengan HD, Thibault G, Li JS, et al.: Resistance artery mechanics, structure, and extracellular components in spontaneously hypertensive rats effects of angiotensin receptor antagonism and converting enzyme inhibition. Circulation 1999, 100:2267–2275. This study showed for the first time that alterations in integrins are associated with extracellular matrix changes and that these alterations may be important determinants in the organization of the structure and mechanical properties of small arteries in patients with hypertension.

    PubMed  CAS  Google Scholar 

  55. Sharifi AM, Li JS, Endemann D, et al.: Comparison of effects of the angiotensin converting enzyme inhibitor enalapril and the calcium channel antagonist amlodipine on small artery structure and composition, and on endothelial dysfunction in SHR. J Hypertens 1998, 16:457–466. This study demonstrated that calcium channel blockade or ACE inhibition can lead to regression of collagen deposition in small arteries from genetically hypertensive rats.

    PubMed  CAS  Google Scholar 

  56. Intengan HD, Deng LY, Li JS, et al.: Mechanics and composition of human subcutaneous resistance arteries in essential hypertension. Hypertension 1999, 33(part II):366–372. This was the first study to demonstrate increased collagen deposition in the small arteries of hypertensive patients. Early in human hypertension, stiffness of the vascular wall may be reduced despite this.

    Google Scholar 

  57. Sharifi AM, Schiffrin EL: Apoptosis in vasculature of spontaneously hypertensive rats: effect of an angiotensin converting enzyme inhibitor and a calcium channel antagonist. Am J Hypertens 1998, 11:1108–1116.

    PubMed  CAS  Google Scholar 

  58. Aalkjaer C, Heagerty AM, Petersen KK, et al.: Evidence for increased media thickness, increased neuronal amine uptake, and depressed excitation-contraction coupling in isolated resistance vessels from essential hypertensives. Circ Res 1987, 61:181–186.

    PubMed  CAS  Google Scholar 

  59. Schiffrin EL, Deng LY, Larochelle P: Blunted effects of endothelin upon small subcutaneous resistance arteries of mild essential hypertensive patients. J Hypertens 1992, 10:437–44.

    PubMed  CAS  Google Scholar 

  60. Lockette W, Otsuka Y, Carretero O: The loss of endotheliumdependent vascular relaxation in hypertension. Hypertension 1986, 8(suppl 2):II61-II66.

    PubMed  CAS  Google Scholar 

  61. Deng LY, Li JS, Schiffrin EL: Endothelium-dependent relaxation of small arteries from essential hypertensive patients. Clin Sci 1995, 88:611–622.

    PubMed  CAS  Google Scholar 

  62. Panza JA, Quyyumi AA, Brush JE, et al.: Abnormal endothelium dependent vascular relaxation in patients with essential hypertension. N Engl J Med 1990, 323:22–27.

    PubMed  CAS  Google Scholar 

  63. Tschudi MR, Mesaros S, Lüscher TF, et al.: Direct in situ measurement of nitric oxide in mesenteric resistance arteries. Hypertension 1996, 27:32–35.

    PubMed  CAS  Google Scholar 

  64. Hoshino J, Nakamura T, Kurashina T, et al.: Antagonism of ANG II type 1 receptors protects the endothelium during the early stages of renal hypertension in rats. Am J Physiol 1998, 275(Pt 2):R1950–1957.

    PubMed  CAS  Google Scholar 

  65. Benetos A, Levy BI, Lacolley P, et al.: Role of angiotensin II and bradykinin on aortic collagen following converting enzyme inhibition in spontaneously hypertensive rats. Arterioscler Thromb Vasc Biol 1997, 17:3196–3201.

    PubMed  CAS  Google Scholar 

  66. Nishikawa K: Angiotensin AT1 receptor antagonism and protection against cardiovascular end-organ damage. J Hum Hypertens 1998, 12:301–309.

    PubMed  CAS  Google Scholar 

  67. Koffi I, Lacolley P, Kirchengaast M, et al.: Prevention of arterial structural alterations with verapamil and trandolapril and consequences for mechanical properties in spontaneously hypertensive rats. Eur J Pharmacol 1998, 361:51–60.

    PubMed  CAS  Google Scholar 

  68. Ceiler DL, Nelissen-Vrancken HJ, De Mey JG, et al.: Effect of chronic blockade of angiotensin II-receptor subtypes on aortic compliance in rats with myocardial infarction. J Cardiovasc Pharmacol 1998, 31:630–637.

    PubMed  CAS  Google Scholar 

  69. Makki T, Talom RT, Niederhoffer N, et al.: Increased arterial distensibility induced by the angiotensin-converting enzyme inhibitor, lisinopril, in normotensive rats. Br J Pharmacol 1994, 111:555–560.

    PubMed  CAS  Google Scholar 

  70. Borhani NO, Mercuri M, Borhani PA, et al.: Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial. JAMA 1996, 276:785–791.

    PubMed  CAS  Google Scholar 

  71. Zanchetti A, Rosei EA, Dal Palu C, et al.: The Verapamil in Hypertension and Atherosclerosis Study (VHAS): results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness. J Hypertens 1998, 16:1667–1676.

    PubMed  CAS  Google Scholar 

  72. Anderson TJ, Elstein E, Haber H, et al.: Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF study). J Am Coll Cardiol 2000, 35:60–66.

    PubMed  CAS  Google Scholar 

  73. Taddei S, Virdis A, Ghiadoni L, et al.: Antihypertensive drugs and reversing of endothelial dysfunction in hypertension. Curr Hypertens Rep 2000, 2:64–70.

    PubMed  CAS  Google Scholar 

  74. Dohi Y, Criscione L, Pfeiffer K, et al.: Angiotensin blockade or calcium antagonists improve endothelial dysfunction in hypertension: studies in perfused mesenteric resistance arteries. J Cardiovasc Pharmacol 1994, 24:372–379.

    PubMed  CAS  Google Scholar 

  75. Li JS, Schiffrin EL: Effect of calcium channel blockade or angiotensin converting enzyme inhibition on structure of coronary, renal and other small arteries in SHR. J Cardiovasc Pharmacol 1996, 28:68–74.

    PubMed  CAS  Google Scholar 

  76. Harrap SB, Van der Merwe WM, Griffin SA, et al.: Brief angiotensin converting enzyme inhibitor treatment in young spontaneously hypertensive rats reduces blood pressure long-term. Hypertension 1990, 16:603–614.

    PubMed  CAS  Google Scholar 

  77. Deng LY, Schiffrin EL: Effect of antihypertensive treatment on response to endothelin of resistance arteries of hypertensive rats. J Cardiovasc Pharmacol 1993, 21:725–731.

    PubMed  CAS  Google Scholar 

  78. Thybo NK, Korsgaard N, Eriksen S, et al.: Dose-dependent effects of perindopril on blood pressure and small-artery structure. Hypertension 1994, 23:659–666.

    PubMed  CAS  Google Scholar 

  79. Rizzoni D, Castellano M, Porteri E, et al.: Effects of low and high doses of fosinopril on the structure and function of resistance arteries. Hypertension 1995, 26:118–123.

    PubMed  CAS  Google Scholar 

  80. Shaw LM, George PR, Oldham AA, et al.: A comparison of the effect of angiotensin converting enzyme inhibition and angiotensin II receptor antagonism on the structural changes associated with hypertension in rat small arteries. J Hypertens 1995, 13:1135–1143.

    PubMed  CAS  Google Scholar 

  81. Li JS, Sharifi MA, Schiffrin EL: Effect of AT1 angiotensin receptor blockade on structure and function of small arteries in SHR. J Cardiovasc Pharmacol 1997, 30:75–83. This in vivo study demonstrated that the growth-promoting effects of angiotensin II on blood vessels are mediated by the AT1 angiotensin receptor subtype.

    PubMed  CAS  Google Scholar 

  82. Li JS, Touyz RM, Schiffrin EL: Effect of AT1 and AT2 angiotensin receptor antagonists in angiotensin II-infused rats. Hypertension 1998, 31(part 2):487–492.

    PubMed  CAS  Google Scholar 

  83. Siragy HM, Carey RM: The subtype-2 (AT2) angiotensin receptor regulates renal cyclic guanosine 3’,5’-monophosphate and AT1 receptor-mediated prostaglandin E2 production in conscious rats. J Clin Invest 1996, 97:1978–1982.

    Article  PubMed  CAS  Google Scholar 

  84. Stoll M, Steckelings UM, Paul M, et al.: The angiotensin AT2 receptor mediates inhibition of cell proliferation in coronary endothelial cells. J Clin Invest 1995, 95:651–657.

    PubMed  CAS  Google Scholar 

  85. Yamada T, Horiuchi M, Dzau VJ: Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci U S A 1996, 93:156–160.

    PubMed  CAS  Google Scholar 

  86. Tsoporis J, Fields N, Lee RM, et al.: Effects of the arterial vasodilator minoxidil on cardiovascular structure and sympathetic activity in spontaneously hypertensive rats. J Hypertens 1993, 11:1337–1345.

    PubMed  CAS  Google Scholar 

  87. Owens GK: Differential effects of antihypertensive drug therapy on vascular smooth muscle cell hypertrophy, hyperploidy, and hyperplasia in the spontaneously hypertensive rat. Circ Res 1985, 56:525–536.

    PubMed  CAS  Google Scholar 

  88. Intengan HD, Schiffrin EL: Disparate effects of carvedilol versus metoprolol treatment of stroke-prone spontaneous hypertensive rats on endothelial function of resistance arteries. J Cardiovasc Pharmacol 2000, in press.

  89. Intengan HD, Schiffrin EL: Vasopeptidase inhibition has potent effects on blood pressure and resistance arteries in SHRSP. Hypertension 2000, in press. This study showed the powerful ability of vasopeptidase inhibition to cause regression of vascular remodeling in severe hypertension in rats.

  90. Schiffrin EL: Endothelin and endothelin antagonists in hypertension. J Hypertens 1998, 16(12 Pt 2):1891–1895.

    PubMed  CAS  Google Scholar 

  91. Sharifi AM, He G, Touyz RM, et al.: Vascular endothelin-1 gene expression and effect of an endothelin A receptor antagonist on structure and function of small arteries from stroke-prone spontaneously hypertensive rats. J Cardiovasc Pharmacol 1998, 31(Suppl 1):S309-S312. This study showed that even in absence of significant lowering of blood pressure, endothelin antagonism can lead to regression of vascular remodeling and at the same time prolong life and reduce events in stroke-prone SHR.

    PubMed  CAS  Google Scholar 

  92. Blezer ELA, Nicolay K, Goldschmeding R, et al.: Early-onset but not late-onset endothelin-A-receptor blockade can modulate hypertension, cerebral edema, and proteinuria in strokeprone hypertensive rats. Hypertension 1999, 33:137–144. This elegant study demonstrated that endothelin receptor antagonism has powerful protective effects on target organ damage in severe genetic hypertension in rats.

    PubMed  CAS  Google Scholar 

  93. 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.

    PubMed  CAS  Google Scholar 

  94. 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 converting enzyme inhibitor. Comparison with effects of a beta blocker. Am J Hypertens 1995, 8:229–236.

    PubMed  CAS  Google Scholar 

  95. Thybo NK, Stephens N, Cooper A, et al.: Efect of antihypertensive treatment on small arteries of patients with previously untreated essential hypertension. Hypertension 1995, 25(part 1):474–481.

    PubMed  CAS  Google Scholar 

  96. Schiffrin EL, Deng LY: Comparison of effects of angiotensin converting enzyme inhibition and beta blockade on function of small arteries from hypertensive patients. Hypertension 1995, 25(part 2):699–703.

    PubMed  CAS  Google Scholar 

  97. 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, 15:197–204.

    PubMed  CAS  Google Scholar 

  98. Schiffrin EL, Park JB, Intengan HD, et al.: Correction of arterial structure and endothelial dysfunction in human essential hypertension by the angiotensin antagonist losartan. Circulation 2000, 101:1653–1659. This study is the first to demonstrate that AT1 antagonism can correct vascular structure and endothelial dysfunction in hypertensive patients, whereas treatment with a b-blocker had no effect.

    PubMed  CAS  Google Scholar 

  99. Padmanabhan N, Jardine AG, McGrath JC, et al.: Angiotensinconverting enzyme-independent contraction to angiotensin I in human resistance arteries. Circulation 1999, 99:2914–2920. This important study showed the potential for generation of angiotensin II by a chymase-like enzyme in human small arteries.

    PubMed  CAS  Google Scholar 

  100. Park JB, Intengan HD, Schiffrin EL: Reduction of resistance artery stiffness by treatment with the AT1 receptor antagonist losartan in essential hypertension. J Renin Angiotens System 2000, 1:in press. This study demonstrated for the first time that treatment with an AT1 antagonist reduced the stiffness of wall components of small arteries in hypertensive patients, whereas treatment with a b-blocker had no effect.

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

    PubMed  CAS  Google Scholar 

  102. Agabiti Rosei E, Rizzoni D, Castellano M, et al.: Media:lumen ratio in human small resistance arteries is related to forearm minimal vascular resistance. J Hypertens 1995, 13:349–355.

    Google Scholar 

  103. Motz W, Strauer BE: Improvement of coronary flow reserve after long-term therapy with enalapril. Hypertension 1996, 27:1031–1038.

    PubMed  CAS  Google Scholar 

  104. Virdis A, Ghiadoni L, Lucarini A, et al.: Presence of cardiovascular structural changes in essential hypertensive patients with coronary microvascular disease and effects of long-term treatment. Am J Hypertens 1996, 9:361–369.

    PubMed  CAS  Google Scholar 

  105. Mancini GBJ, 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, 94:258–265.

    PubMed  CAS  Google Scholar 

  106. Taddei S, Virdis A, Ghiadoni L, et al.: Lacidipine restores endothelium-dependent vasodilation in essential hypertensive patients. Hypertension 1997, 30:1606–1612.

    PubMed  CAS  Google Scholar 

  107. Frielingsdorf J, Seiler C, Kauffmnan P, et al.: Normalization of abnormal coronary vasomotion by calcium antagonists in patients with hypertension. Circulation 1996, 93:1380–1387.

    PubMed  CAS  Google Scholar 

  108. UK Prospective Diabetes Study Group: Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ 1998, 317:713–720. This important 10-year study of diabetic patients suggests that ACE inhibition and b-blockade are equally effective in the treatment of patients with diabetes and hypertension.

    Google Scholar 

  109. Hanson 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, 353:611–616. This randomized clinical trial showed equivalent effects of ACE inhibitors and conventional therapy, although the former were more effective on myocardial ischemic events and the latter on stroke. This effect on stroke may be the consequence of a randomization problem characterized by lower blood pressure in the conventional therapy group throughout the study.

    Google Scholar 

  110. Hansson L, Lindholm LH, Ekbom T, et al.: Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity in the Swedish Trial in Old Patients with Hypertension-2 study. Lancet 1999, 354:1751–1756. This important randomized clinical trial showed that ACE inhibitors are particularly effective at reducing the incidence of acute coronary events in an elderly hypertensive population; this effect may result in part from the vascular protection offered by these agents.

    PubMed  CAS  Google Scholar 

  111. The Heart Outcomes Prevention Evaluation Study Investigators: Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000, 342:145–154. This extremely important study showed that the ACE inhibitor ramipril had a dramatic favorable effect on cardiovascular morbidity and mortality in a 4.5-year multicenter study. This effect may in part be the result of the vascular protective effect of interruption of the renin-angiotensin system.

    Google Scholar 

  112. Lever AF, Beevers DG, Hole DJ, et al.: Mortality amongst patients of the Glasgow blood pressure clinic was high in the 1970s and 80s but has fallen since, why? Clin Exp Hypertens 1999, 21:553–562. This important retrospective study demonstrated that mortality has been reduced in this hypertension clinic since introduction of calcium channel antagonists and ACE inhibitors, and that this reduction appears mostly related to use of the latter.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Park, J.B., Schiffrin, E.L. Effects of antihypertensive therapy on hypertensive vascular disease. Current Science Inc 2, 280–288 (2000). https://doi.org/10.1007/s11906-000-0011-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-000-0011-5

Keywords

Navigation