American Heart Journal
Volume 156, Issue 6 , Pages 1154.e1-1154.e8 , December 2008

Long-term treatment with sulfhydryl angiotensin-converting enzyme inhibition reduces carotid intima-media thickening and improves the nitric oxide/oxidative stress pathways in newly diagnosed patients with mild to moderate primary hypertension

  • Claudio Napoli, MD, PhD, MBEth, FACA

      Affiliations

    • Department of General Pathology and Excellence Research Center on Cardiovascular Diseases, and Microbiology Section, 1st School of Medicine, II University of Naples, Naples, Italy
    • IRCCS, Multimedica, Milan, Italy
    • Corresponding Author InformationReprint requests: Professor Claudio Napoli, MD, PhD, MBEth, FACA, Department of General Pathology and Excellence Research Center on Cardiovascular Diseases, 1st School of Medicine, II University of Naples; Complesso S. Andrea delle Dame; Via L. de Crecchio 7, Naples, 80138, Italy.
    • ,
  • Giuseppe Bruzzese, MD

      Affiliations

    • Division of Cardiology-UTIC, Pellegrini Hospital, ASLNA1, Naples, Italy
    • ,
  • Louis J. Ignarro, PhD

      Affiliations

    • Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA
    • ,
  • Ettore Crimi, MD

      Affiliations

    • Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA
    • ,
  • Filomena de Nigris, BiolD, PhD

      Affiliations

    • Department of General Pathology and Excellence Research Center on Cardiovascular Diseases, and Microbiology Section, 1st School of Medicine, II University of Naples, Naples, Italy
    • ,
  • Sharon Williams-Ignarro, MD

      Affiliations

    • Division of Anesthesiology and, David Geffen School of Medicine, University of California, Los Angeles, CA
    • ,
  • Sabina Libardi, BS

      Affiliations

    • IRCCS, Multimedica, Milan, Italy
    • ,
  • Linda Sommese, BiolD

      Affiliations

    • Department of General Pathology and Excellence Research Center on Cardiovascular Diseases, and Microbiology Section, 1st School of Medicine, II University of Naples, Naples, Italy
    • ,
  • Carmela Fiorito, BS

      Affiliations

    • IRCCS, Multimedica, Milan, Italy
    • ,
  • Francesco P. Mancini, MD, PhD

      Affiliations

    • Department of Biological and Environmental Sciences, University of Sannio, Benevento, Italy
    • ,
  • Francesco Cacciatore, MD, PhD, MPH

      Affiliations

    • Fondazione Salvatore Maugeri, IRCCS, Telese Terme (BN), Italy
    • ,
  • Antonio Liguori, MD

      Affiliations

    • Division of Cardiology-UTIC, Pellegrini Hospital, ASLNA1, Naples, Italy

Received 24 June 2008 ,Accepted 10 September 2008.

References 

  1. Ambrosioni E. Defining the role of zofenopril in the management of hypertension and ischemic heart disorders. Am J Cardiovasc Drugs. 2007;7:17–24
  2. Napoli C, Loscalzo J. New challenges for ACE-inhibitors in vascular diseases. Drug Design Rev. 2005;2:485–493
  3. Napoli C, Sica V, Pignalosa O, et al. New trends in anti-atherosclerotic agents. Curr Med Chem. 2005;12:1755–1772
  4. Pasini AF, Garbin U, Nava MC, et al. Effect of sulfhydryl and non-sulfhydryl angiotensin-converting enzyme inhibitors on endothelial function in essential hypertensive patients. Am J Hypertens. 2007;20:443–450
  5. Powell JS, Clozel JP, Müller RK, et al. Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury. Science. 1989;245:186–188
  6. Janiak P, Libert O, Vilaine JP. Role of the renin-angiotensin system in neointima formation after injury in rabbits. Hypertension. 1994;24:671–678
  7. Fennessy PA, Campbell JH, Campbell GR. Perindopril inhibits both the development of atherosclerosis in the cholesterol-fed rabbit and lipoprotein binding to smooth muscle cells in culture. Atherosclerosis. 1994;106:29–41
  8. Smith SC, Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation. 2006;113:2363–2372
  9. Napoli C, Cicala C, D'Armiento FP, et al. Beneficial effects of ACE-inhibition with zofenopril on plaque formation and low-density lipoprotein oxidation in Watanabe heritable hyperlipidemic rabbits. Gen Pharmacol. 1999;33:467–477
  10. Chobanian AV, Haudenschild CC, Nickerson C, et al. Antiatherogenic effect of captopril in the Watanabe heritable hyperlipidemic rabbit. Hypertension. 1990;15:327–331
  11. Aberg G, Ferrer P. Effects of captopril on atherosclerosis in cynomolgus monkeys. J Cardiovasc Pharmacol. 1990;15:S65–S72
  12. Hayek T, Attias J, Smith J, et al. Antiatherosclerotic and antioxidative effects of captopril in apolipoprotein E-deficient mice. J Cardiovasc Pharmacol. 1998;31:540–544
  13. de Nigris F, D'Armiento FP, Somma P, et al. Chronic treatment with sulfhydryl angiotensin-converting enzyme inhibitors reduce susceptibility of plasma LDL to in vitro oxidation, formation of oxidation-specific epitopes in the arterial wall, and atherogenesis in apolipoprotein E knockout mice. Int J Cardiol. 2001;81:107–115
  14. Sun YP, Zhu BQ, Browne AE, et al. Comparative effects of ACE inhibitors and an angiotensin receptor blocker on atherosclerosis and vascular function. J Cardiovasc Pharmacol Ther. 2001;6:175–181
  15. Charpiot P, Rolland PH, Friggi A, et al. ACE inhibition with perindopril and atherogenesis-induced structural and functional changes in minipig arteries. Arterioscler Thromb. 1993;13:1125–1138
  16. Candido R, Jandeleit-Dahm KA, Cao Z, et al. Prevention of accelerated atherosclerosis by angiotensin-converting enzyme inhibition in diabetic apolipoprotein E-deficient mice. Circulation. 2002;106:246–253
  17. Kowala MC, Grove RI, Aberg G. Inhibitors of angiotensin converting enzyme decrease early atherosclerosis in hyperlipidemic hamsters. Fosinopril reduces plasma cholesterol and captopril inhibits macrophage-foam cell accumulation independently of blood pressure and plasma lipids. Atherosclerosis. 1994;108:61–72
  18. Hayek T, Attias J, Coleman R, et al. The angiotensin-converting enzyme inhibitor, fosinopril, and the angiotensin II receptor antagonist, losartan, inhibit LDL oxidation and attenuate atherosclerosis independent of lowering blood pressure in apolipoprotein E deficient mice. Cardiovasc Res. 1999;44:579–587
  19. Li J, Hirose N, Kawamura M, et al. Antiatherogenic effect of angiotensin converting enzyme inhibitor (benazepril) and angiotensin II receptor antagonist (valsartan) in the cholesterol-fed rabbits. Atherosclerosis. 1999;143:315–326
  20. Keidar S, Attias J, Coleman R, et al. Attenuation of atherosclerosis in apolipoprotein E-deficient mice by ramipril is dissociated from its antihypertensive effect and from potentiation of bradykinin. J Cardiovasc Pharmacol. 2000;35:64–72
  21. Hayek T, Kaplan M, Raz A, et al. Ramipril administration to atherosclerotic mice reduces oxidized low-density lipoprotein uptake by their macrophages and blocks the progression of atherosclerosis. Atherosclerosis. 2002;161:65–74
  22. Bonithon-Kopp C, Ducimetière P, Touboul PJ, et al. Plasma angiotensin-converting enzyme activity and carotid wall thickening. Circulation. 1994;89:952–954
  23. MacMahon S, Sharpe N, Gamble G, et al. Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease: PART-2 Collaborative Research Group. Prevention of Atherosclerosis with Ramipril. J Am Coll Cardiol. 2000;36:438–443
  24. Teo KK, Burton JR, Buller CE, et al. Long-term effects of cholesterol lowering, and angiotensin-converting enzyme inhibition on coronary atherosclerosis: the simvastatin/enalapril coronary atherosclerosis trial. Circulation. 2000;102:1748–1754
  25. Asselbergs FW, van Roon AM, Hillege HL, et al. Effects of fosinopril and pravastatin on carotid intima-media thickness in subjects with increased albuminuria. Stroke. 2005;36:649–653
  26. Zanchetti A, Crepaldi G, Bond MG, et al. on behalf of PHYLLIS Investigators Different effects of antihypertensive regimens based on fosinopril or hydrochlorothiazide with or without lipid lowering by pravastatin on progression of asymptomatic carotid atherosclerosis: principal results of PHYLLIS—a randomized double-blind trial. Stroke. 2004;35:2807–2812
  27. Lonn EM, Yusuf S, Dzavik V, et al. Effects of ramipril and vitamin E on atherosclerosis: the Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE). Circulation. 2001;103:919–925
  28. Unger T. the role of the renin-angiotensin system in the development of cardiovascular disease. Am J Cardiol. 2002;89:3A–10A
  29. Jacoby DS, Rader DJ. Renin-angiotensin system and atherothrombotic disease: from genes to treatment. Arch Intern Med. 2003;163:1155–1164
  30. Scribner AW, Loscalzo J, Napoli C. The effect of angiotensin converting enzyme inhibition on endothelial function and oxidant stress. Eur J Pharmacol. 2003;482:95–99
  31. Napoli C, Sica V, de Nigris F, et al. Sulfhydryl ACE inhibition induces a sustained reduction of systemic oxidative stress and improves the nitric oxide pathway in patients with essential hypertension. Am Heart J. 2004;148:e5–e13
  32. Evangelista S, Manzini S. Antioxidant and cardioprotective properties of the sulphydryl angiotensin-converting enzyme inhibitor zofenopril. J Int Med Res. 2005;33:42–54
  33. Cominacini L, Pasini A, Garbin U, et al. Zofenopril inhibits the expression of adhesion molecules on endothelial cells by reducing reactive oxygen species. Am J Hypertens. 2002;15:891–895
  34. Grobbee DE, Bots ML. Carotid artery intima-media thickness as an indicator of generalized atherosclerosis. J Intern Med. 1994;263:567–573
  35. O'Leary DH, Polak JF, Kronmal RA, et al. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Eng J Med. 1999;340:14–22
  36. Napoli C, Lerman LO, de Nigris F, et al. Rethinking primary prevention of atherosclerosis-related diseases. Circulation. 2006;114:2517–2527
  37. Napoli C, Liguori A, Sorice P, et al. Relations between vasoactive hormonal factors and left ventricular diastolic function in normotensive and hypertensive uremics. J Intern Med. 1996;240:389–394
  38. Persson J, Stavenow L, Wikstrand J, et al. Noninvasive quantification of atherosclerotic lesions. Reproducibility of ultrasonographic measurements of arterial wall thickness and plaque size. Arterioscler Thromb. 1992;12:261–266
  39. Burke GL, Evans GW, Riley WA, et al. Arterial wall thickness is associated with prevalent cardiovascular disease in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Stroke. 1995;26:386–391
  40. Allan PL, Mowbray PI, Lee AJ, et al. Relationship between carotid intima-media thickness and symptomatic and asymptomatic peripheral arterial disease: the Edinburgh Artery Study. Stroke. 1997;28:348–353
  41. Yusuf S, Sleight P, Pogue J, et al. for 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;342:145–153
  42. Wang JG, Staessen JA, Li Y, et al. Carotid intima-media thickness and antihypertensive treatment. A meta-analysis of randomized controlled trials. Stroke. 2006;37:1933–1940
  43. Hosomi N, Mizushige K, Ohyama H, et al. Angiotensin-converting enzyme inhibition with enalapril slows progressive intima-media thickening of the common carotid artery in patients with non–insulin-dependent diabetes mellitus. Stroke. 2001;32:1539–1545
  44. Espeland MA, Craven TE, Riley WA, et al. for the Asymptomatic Carotid Artery Progression Study Research Group Reliability of longitudinal ultrasonographic measurements of carotid intimal-medial thicknesses. Stroke. 1996;27:480–485
  45. Glagov S, Weisenberg E, Zarins CK, et al. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med. 1987;316:1371–1375
  46. Cashin-Hemphill L, Holmvang G, Chan RC, et al. for the QUIET Investigators (Quinapril Ischemic Event Trial). Angiotensin-converting enzyme inhibition as antiatherosclerotic therapy: no answer yet. Am J Cardiol. 1999;83:43–47
  47. Hornig B, Arakawa N, Haussmann D, et al. Differential effects of quinaprilat and enalaprilat on endothelial function of conduit arteries in patients with chronic heart failure. Circulation. 1998;98:2842–2848
  48. Burnier M, Zanchi A. Blockade of renin-angiotensin-aldosterone system: a key therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes. J Hypertens. 2006;24:11–25
  49. Kurtz TW, Pravenec M. Antidiabetic mechanisms of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists: beyond the renin-angiotensin system. J Hypertens. 2004;22:2253–2261
  50. Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. Lancet. 1995;345:669–685
  51. Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet. 1994;343:1115–11122
  52. Mak IT, Freedman AM, Dickens BF, et al. Protective effects of sulfhydryl-containing angiotensin-converting enzyme inhibitors against free radical injury in endothelial cells. Biochem Pharmacol. 1990;40:2169–2175
  53. Ambrosioni E, Borghi C, Magnani B. The effect of angiotensin-converting–enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. N Engl J Med. 1995;332:80–85
  54. Borghi C, Bacchelli S, Esposti DD, et al. Effects of the administration of an angiotensin-converting enzyme inhibitor during the acute phase of myocardial infarction in patients with arterial hypertension. SMILE Study Investigators. Survival of Myocardial Infarction Long-term Evaluation. Am J Hypertens. 1999;12:665–672
  55. Borghi C, Ambrosioni E. Double-blind comparison between zofenopril and lisinopril in patients with acute myocardial infarction: results of the Survival of Myocardial Infarction Long-Term Evaluation-2 (SMILE-2) study. Am Heart J. 2003;145:80–87
  56. Napoli C, Ignarro LJ. Nitric oxide and atherosclerosis. Nitric Oxide. 2001;5:88–97
  57. Furuki K, Adachi H, Matsuoka H, et al. Plasma levels of asymmetric dimethylarginine (ADMA) are related to intima-media thickness of the carotid artery. An epidemiological study. Atherosclerosis. 2007;191:206–210

 Presented in abstract form at the Symposium “Current role of angiotensin converting enzyme-inhibitors in high-risk patients,” European Society of Cardiology, September 1, 2003, Wien (Austria); at the Plenary Session on ACE-Inhibition, 65° National Congress of the Italian Society of Cardiology, December 13, 2004, Rome, Italy; at the Plenary Session on “The renin angiotensin system and oxidative stress,” 4° International Forum on Angiotensin II Receptor Antagonism, January 28, 2005, Monte Carlo, Monaco; and at the Annual Meeting of European Society of Atherosclerosis, June 10, 2007, Helsinki, Finland.

PII: S0002-8703(08)00791-6

doi: 10.1016/j.ahj.2008.09.006

American Heart Journal
Volume 156, Issue 6 , Pages 1154.e1-1154.e8 , December 2008

Article Tools

* Image Usage & Resolution