The effect of antihypertensive drugs on vascular compliance

  • Nathaniel Winer
  • Michael A. Weber
  • James R. Sowers


Measurement of vascular compliance has assumed increasing importance as a marker of early disease of the vascular wall, a predictor of future vascular disease, and a way to monitor the effects of vasoactive agents on arterial wall stiffness. Vascular compliance can be estimated by several methods: measurement of the pulse pressure, or pulse pressure-stroke volume ratio; analysis of the systolic pulse wave augmentation index and the diastolic pulse wave contour; ultrasonic echo-tracking; and MRI. Because few comparative studies have been done, the physiologic significance of the measures of compliance obtained by each method is uncertain. Antihypertensive drugs may improve vascular compliance by reducing blood pressure, relaxing vascular smooth muscle, or promoting long-term effects on vascular smooth muscle and cardiomyocyte growth and remodeling. Angiotensin converting enzyme (ACE) inhibitors have been reported to improve vascular compliance in nearly all studies, suggesting a beneficial class effect independent of blood pressure reduction. Favorable changes in the vascular wall-lumen ratio of small vessels from subcutaneous gluteal biopsy specimens after treatment with ACE inhibitors and the persistence of improved vascular compliance after withdrawal of therapy indicate that these agents may produce long-term vascular remodeling. Although few studies have been done, angiotensin II receptor antagonists improve vascular compliance, possibly by blocking angiotensin II-mediated cell proliferation and increasing apoptosis via unopposed AT1 receptor stimulation. In contrast, calcium antagonists and b-blockers have variable effects on vascular compliance, although b-blockers with intrinsic sympathomimetic activity improve vascular compliance. Diuretics have little effect on vascular compliance beyond their blood pressure-lowering actions, except for spironolactone, which by improving vascular compliance may have contributed to the reduction in heart failure mortality seen in the Randomized Aldactone Evaluation Study.

References and Recommended Readings

  1. 1.
    Cohn JN: Arteries, myocardium, blood pressure and cardiovascular risk: towards a revised definition of hypertension. J Hypertens 1998, 16:2117–2124.PubMedGoogle Scholar
  2. 2.
    Panza JA, Quyyumi AA, Callahan TS, et al.: Effect of antihypertensive treatment on endothelium-dependent vascular relaxation in patients with essential hypertension. J Am Coll Cardiol 1993, 21:1145–1151.PubMedGoogle Scholar
  3. 3.
    Gibbons G, Dzau VJ: The emerging concept of vascular remodeling. N Engl J Med 1994, 330:1431–1438.PubMedCrossRefGoogle Scholar
  4. 4.
    MacMahon S, Peto R, Cutler J, et al.: Blood pressure, stroke, and coronary heart disease. Part 1, prolonged differences in blood pressure; prospective observational studies corrected for the regression dilution bias. Lancet 1990, 335:765–774.PubMedCrossRefGoogle Scholar
  5. 5.
    Collins R, Peto R, MacMahon S, et al.: Blood pressure, stroke, and coronary artery disease. Part 2, short term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990, 335:827–839.PubMedCrossRefGoogle Scholar
  6. 6.
    London GM, Guerin AP: Influence of arterial pulse and reflected waves on blood pressure and cardiac function. Am Heart J 1999, 138:S220-S224. This article provides an overview of factors contributing to arterial stiffening and emphasizes the consequences of reduced vascular compliance and reflected waves.CrossRefGoogle Scholar
  7. 7.
    Vaughn MW, Kuo L, Liao JC: Effective diffusion distance of nitric oxide in the microcirculation. Am J Physiol 1998, 274:H1705-H1714.PubMedGoogle Scholar
  8. 8.
    Simon A, Megnien JL, Levenson J: Detection of preclinical atherosclerosis may optimize management of hypertension. Am J Hypertens 1997, 10:813–824.PubMedCrossRefGoogle Scholar
  9. 9.
    Cohn JN: Pathophysiologic and prognostic implications of measuring arterial compliance changes in hypertensive disease. Prog Cardiovasc Dis 1999, 41:441–450. This review contains descriptions and critiques of current techniques for assessing the structure and function of the vasculature and supports the view that arterial wall changes precede vascular events.PubMedCrossRefGoogle Scholar
  10. 10.
    Franklin SS, Sutton-Tyrell K, Belle S, et al.: The importance of pulsatile components of hypertension in predicting carotid stenosis in older adults. J Hypertens 1997, 15:1143–1150.PubMedCrossRefGoogle Scholar
  11. 11.
    Ferguson JJ, Julius S, Randall OS: Stroke volume-pulse pressure relationships in borderline hypertension: a possible indicator of decreased arterial compliance. J Hypertens 1984, 2(suppl 13):397–399.Google Scholar
  12. 12.
    de Simone G, Roman MJ, Koren MJ, et al.: Stroke volume/pulse pressure ratio in arterial hypertension. Hypertension 1999, 33:800–805.PubMedGoogle Scholar
  13. 13.
    Kelly R, Hayward C, Avolio A, et al.: Noninvasive determination of age-related changes in the human arterial pulse. Circulation 1989, 80:1652–1659.PubMedGoogle Scholar
  14. 14.
    Chen C-H, Nevo E, Feltics B, et al.: Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure—validation of generalized transfer function. Circulation 1997, 95:1827–1836.PubMedGoogle Scholar
  15. 15.
    Asmar R, Rudnichi A, Blacher J, et al.: Pulse pressure and aortic pulse wave are markers of cardiovascular risk in hypertensive populations. Am J Hypertens 2001, 14:91–97.PubMedCrossRefGoogle Scholar
  16. 16.
    Cohn JN, Finkelstein SM, McVeigh GE, et al.: Non-invasive pulse wave analysis for the early detection of vascular disease. Hypertension 1995, 26:503–508.PubMedGoogle Scholar
  17. 17.
    Goldwyn RM, Watt TB Jr.: Arterial pulse pressure contour analysis via a mathematical model for the clinical confirmation of human vascular properties. IEEE Trans Biomed Eng 1967, 14:11–17.Google Scholar
  18. 18.
    Gilani M, Alinder C, Kaiser D, et al.: Differences in large and small artery response to acute inhibition of nitric oxide synthase in human subjects [abstract]. Am J Hypertens 2000, 13:187A.CrossRefGoogle Scholar
  19. 19.
    Resnick LM, Militianu D, Cunnings AJ, et al.: Pulse waveform analysis of arterial compliance: relation to other techniques, age, and metabolic variables. Am J Hypertens 2000, 13:1243–1249.PubMedCrossRefGoogle Scholar
  20. 20.
    Cohn JN, Finkelstein SM: Abnormalities of vascular compliance in hypertension, aging, and heart failure. J Hypertens 1992, (suppl 10):S61–S64.Google Scholar
  21. 21.
    Morgan TJ, Olson T, Lemay J, et al.: Arterial vascular compliance in pre- and post-menopausal women and the effect of short-term estrogen replacement [abstract]. Am J Hypertens 1996, 9:6A.CrossRefGoogle Scholar
  22. 22.
    McVeigh GE, Bratteli CW, Morgan DJ, et al.: Age-related abnormalities in arterial compliance identified by pulse pressure contour analysis: aging and arterial compliance. Hypertension 1999, 33:1392–1398.PubMedGoogle Scholar
  23. 23.
    McVeigh GE, Morgan DJ, Finkelstein SM, et al.: Vascular abnormalities associated with long-term cigarette smoking identified by arterial waveform analysis. Am J Med 1997, 102:227–231.PubMedCrossRefGoogle Scholar
  24. 24.
    McVeigh GE, Brennan GM, Finklestein SM, et al.: Fish oil improves arterial compliance in non-insulin-dependent diabetes mellitus. Arterioscler Thromb 1994, 14:1425–1429.PubMedGoogle Scholar
  25. 25.
    McVeigh GE, Brennan GM, Finklestein SM, et al.: Fish oil improves arterial compliance in non-insulin-dependent diabetes mellitus. Arterioscler Thromb 1994, 14:1425–1429.PubMedGoogle Scholar
  26. 26.
    Glasser SP, Arnett DK, McVeigh GE, et al.: The importance of arterial compliance in cardiovascular drug therapy. J Clin Pharmacol 1998, 38:202–212. The authors define vascular compliance, including the Windkessel concept, and provide a comprehensive review of the effects of antihypertensive drugs on vascular compliance.PubMedGoogle Scholar
  27. 27.
    Tardy Y, Meister JJ, Perret F, et al.: Non-invasive estimate of the mechanical properties of peripheral arteries from ultrasonic and photoplethysmographic measurements. Clin Phys Physiol Meas 1991, 12:39–54.PubMedCrossRefGoogle Scholar
  28. 28.
    Winer N, Weber MA, Sowers JR: Gender differences in vascular compliance in young, healthy subjects. Clin Hypertens 2001, In press.Google Scholar
  29. 29.
    Molhiaddin RH, Underwood SR, Bogren HG, et al.: Regional aortic compliance studied by magnetic resonance imaging: the effects of age, training, and coronary artery disease. Br Heart J 1989, 62:90–96.Google Scholar
  30. 30.
    Aalkjaer D, 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.PubMedGoogle Scholar
  31. 31.
    Bank AJ, Wilson RF, Kubo SH, et al.: Direct effects of smooth muscle relaxation and contraction on in vivo human brachial artery elastic properties. Circulation 1995, 77:1008–1016.Google Scholar
  32. 32.
    Glasser SP, Selwyn AP, Ganz P, et al.: Vascular compliance a nd cardiovascular disease: a risk factor or a marker? Am J Hypertens 1997, 10:1175–1189.PubMedCrossRefGoogle Scholar
  33. 33.
    Van Bortel LM, Kool Boudier HAS: Effects of antihypertensive agents on local arterial distensibility and compliance. Hypertension 1995, 26:531–534.PubMedGoogle Scholar
  34. 34.
    Kool MJ, Lustermans FA, Breed JG, et al.: Effect of perindopril and amiloride/hydrochlorothiazide on haemodynamic and vessel wall properties of large arteries. J Hypertens 1993, 11:S362-S363.CrossRefGoogle Scholar
  35. 35.
    London GM, Pannier B, Guerin AP, et al.: Cardiac hypertrophy, aortic compliance, peripheral resistance, and wave reflection in end-stage renal disease: comparative effects of ACE inhibition and calcium channel blockade. Circulation 1994, 90:2786–2796.PubMedGoogle Scholar
  36. 36.
    Thybo NK, Stephens N, Cooper A, et al.: Effect of antihypertensive treatment on small arteries of patients with previously untreated essential hypertension. Hypertension 1995, 25 (Pt 1):474–481.PubMedGoogle Scholar
  37. 37.
    De Cesaris R, Ranieri G, Filitti V, et al.: Forearm distensibility in patients with hypertension: comparative effects of long-term ACE inhibition and beta-blocking. J Clin Pharm Ther 1993, 53:360–367.Google Scholar
  38. 38.
    Shimamoto H, Shimamoto Y: Lisinopril improves aortic compliance and renal flow: comparison with nifedipine. Hypertension 1995, 25:327–334.PubMedGoogle Scholar
  39. 39.
    Perret F, Mooser V, Hayoz D, et al.: Evaluation of arterial compliance-pressure curves. Effect of antihypertensive drugs. Hypertension 1991, 18(4 suppl):II77-II83.PubMedGoogle Scholar
  40. 40.
    De Luca N, Rosiello G, Lamenza F, et al.: Reversal of cardiac and large artery structural abnormalities induced by long-term antihypertensive treatment with trandolopril. Am J Cardiol 1992, 70:52D-59D.PubMedCrossRefGoogle Scholar
  41. 41.
    Breithaupt-Grogler K, Leschinger M, Belz GG, et al.: Influence of antihypertensive therapy with cilazapril and hydrochlorothiazide on the stiffness of the aorta. Cardiovasc Drugs Ther 1996, 10:49–57.PubMedGoogle Scholar
  42. 42.
    Schartl M, Boksch WG, Dreysse S, et al.: Remodeling of myocardium and arteries by chronic angiotensin converting enzyme inhibition in hypertensive patients. J Hypertens 1994, 12(suppl 4):S37-S42.Google Scholar
  43. 43.
    Soma J, Aakhus S, Dahl K, et al.: Total arterial compliance during selective beta1-adrenergic receptor blockade and angiotensin-converting enzyme inhibition. J Cardiovasc Pharm 1999, 33:273–279.CrossRefGoogle Scholar
  44. 44.
    Chen CH, Ting CT, Lin SJ, et al.: Different effects of fosinopril and atenolol on wave reflections in hypertensive patients. Hypertension 1995, 25:1034–1041.PubMedGoogle Scholar
  45. 45.
    Klemsdal TO, Moan A, Kjeldsen SE: Effects of selective angiotensin II type 1 receptor blockade with losartan on arterial compliance in patients with mild essential hypertension. Blood Press 1999, 8:214–219.PubMedCrossRefGoogle Scholar
  46. 46.
    Schriffrin EL, Park JB, Intengan HD, et al.: Correction of arterial structure and endothelial function in human essential hypertension by the angiotensin receptor antagonist losartan. Circulation 2000, 101:1653–1659. This study shows that 1-year treatment with the angiotensin II receptor antagonist, losartan, effectively normalizes the altered structure and endothelial dysfunction of resistance arteries from patients with essential hypertension, whereas atenolol has no effect.Google Scholar
  47. 47.
    Mahmud A, Feely J: Favorable effects on arterial wave reflection and pulse pressure amplification of adding angiotensin II receptor blockade in resistant hypertension. J Hum Hypertens 2000, 14:541–546.PubMedCrossRefGoogle Scholar
  48. 48.
    Franklin SS: Is there a preferred antihypertensive therapy for isolated systolic hypertension and reduced arterial compliance? Curr Hypertens Rep 2000, 2:253–259.PubMedCrossRefGoogle Scholar
  49. 49.
    Pancera P, Arosio A, Arcaro G, et al.: Hemodynamic properties in hypertensive patients: changes induced by lacidipine and nifedipine. J Hypertens 1989, 7:284–285.Google Scholar
  50. 50.
    Wysocki M, Persson B, Bagge U, et al.: Flow resistance and its components in hypertensive men treated with the calcium antagonist isradipine. Eur J Clin Pharmacol 1992, 43:463–468.PubMedCrossRefGoogle Scholar
  51. 51.
    Schmieder RE, Messerli FH: The compliance of the large elastic arteries after blood pressure-lowering therapy with a calcium antagonist. Dtsche Med Wochenschr 1995, 120:907–911.Google Scholar
  52. 52.
    Ting C-T, Chen JW, Chang MS, et al.: Arterial hemodynamics in human hypertension. Effects of the calcium channel antagonist, nifedipine. Hypertension 1995, 25:327–334.Google Scholar
  53. 53.
    Safar M, Bons J, Georges D, et al.: Calcium blocker lacipine and carotid arteriolar vasodilation in healthy volunteers. Clin Pharmacol Ther 1989, 46:94–98.PubMedGoogle Scholar
  54. 54.
    Pannier BM, Lafleche AB, Girerd XJ, et al.: Arterial stiffness and wave reflections following acute calcium blockade in essential hypertension. Am J Hypertens 1994, 7:168–176.PubMedGoogle Scholar
  55. 55.
    van Merode T, van Bortel LM, Smeets FA, et al.: Verapamil and nebivolol improve carotid artery distensibility in hypertensive patients. J Hypertens 1989, 7:S262-S263.Google Scholar
  56. 56.
    Asmar R, Benetos A, Brahimi M, et al.: Arterial and hypertensive effects of nitrendipine: a double-blind comparison versus placebo. J Cardiovasc Pharmacol 1992, 20:858–863.PubMedCrossRefGoogle Scholar
  57. 57.
    Chau NP, Simon A, Vijar J, et al.: Active and passive effects of antihypertensive drugs on large artery diameter and elasticity in human essential hypertension. J Cardiovasc Pharmacol 1992, 19:78–85.PubMedCrossRefGoogle Scholar
  58. 58.
    Khder Y, Bray des Boscs L, el Ghawi R, et al.: Calcium antagonists and thiazide diuretics have opposite effects on blood rheology and radial artery compliance in arterial hypertension. Fund Clin Pharmacol 1998, 12:457–462.CrossRefGoogle Scholar
  59. 59.
    Tavli T, Kozan O, Cin VG, et al.: The effect of nisoldipine on carotid artery stiffness and left ventricular functions. Jpn Heart J 1995, 36:629–637.PubMedGoogle Scholar
  60. 60.
    De Cesaris R, Ranieri G, Filitti V et al.: Large artery compliance in essential hypertension. Effects of calcium antagonism and beta-blocking. Am J Hypertens 1992, 5:624–628.PubMedGoogle Scholar
  61. 61.
    Kahonen M, Ylitalo R, Koobi T, et al.: Influence of captopril, propranolol, and verapamil on arterial pulse wave velocity and other cardiovascular parameters in healthy volunteers. Int J Clin Pharmacol Ther 1998, 36:483–489.PubMedGoogle Scholar
  62. 62.
    Safar ME, Simon AC, Levenson JA, et al.: Hemodynamic effects of diltiazem in hypertension. Circ Res 1983, 52(suppl I):I–169-I-173.Google Scholar
  63. 63.
    Levenson JA, Simon AC, Zabludowski JE: Effects of betaadrenergic blockade on the arterial vasculature in essential hypertension. Am J Nephrol 1986, 6(suppl 2):88–93.PubMedCrossRefGoogle Scholar
  64. 64.
    De Cesaris R, Ranieri G, Filitti V, et al.: Forearm distensibility in patients with hypertension: comparative effects of long-term ACE inhibition and beta-blocking. Clin Pharmacol Ther 1993, 53:360–367.PubMedGoogle Scholar
  65. 65.
    De Luca N, Rossiell G, Crispino M, et al.: Effects of chronic antihypertensive treatment with ketanserin versus metoprolol on blood pressure and large arteries’ compliance in humans: a cross-over double-blind study. J Clin Pharmacol 1988, 28:332–338.PubMedGoogle Scholar
  66. 66.
    Heesen WF, Beltman FW, Smit AJ, et al.: Effect of quinapril and triamterine/hydrochlorothiazide on cardiac and vascular end-organ damage in isolated systolic hypertension. J Cardiovasc Pharmacol 1998, 31:187–194.PubMedCrossRefGoogle Scholar
  67. 67.
    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.PubMedCrossRefGoogle Scholar
  68. 68.
    Levenson J, Gariepy J, Megnien L, et al.: Diuretics and arteriolar resistance and arterial compliance in human hypertension. Eur Heart J 1992, 13(suppl G):S48-S52.Google Scholar
  69. 69.
    Lagrue G, Ansquer JC, Meyer-Heine A: Peripheral action of spironolactone: improvement in arterial elasticity. Am J Cardiol 1990, 65:9K-11K.PubMedCrossRefGoogle Scholar
  70. 70.
    Duprez DA, DuBuyzere ML, Reitzchel ER, et al.: Inverse relationship between aldosterone and large artery compliance in chronically treated heart failure patients. Eur Heart J 1998, 19:1371–1376. Aldosterone levels may play an important role in reducing vascular compliance.PubMedCrossRefGoogle Scholar
  71. 71.
    Pitt B, Zannad F, Remme WJ, et al.: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999, 341:709–717.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2001

Authors and Affiliations

  • Nathaniel Winer
    • 1
  • Michael A. Weber
    • 1
  • James R. Sowers
    • 1
  1. 1.Division of Endocrinology, Diabetes, and HypertensionSUNY Downstate Medical CenterBrooklynUSA

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