Skip to main content
SpringerLink
Log in
Book cover

ACE Inhibitors pp 71–79Cite as

Birkhäuser

The role of ACE inhibition in heart failure

  • Chapter

Part of the book series: Milestones in Drug Therapy MDT ((MDT))

Abstract

In the early 1970s, ACE inhibition was viewed as an effective means to block the renin-angiotensin component contributing to the maintenance of vasoconstriction [1]. Earlier work had already demonstrated the activation of the renin angiotensin system (RAS) in decompensated congestive heart failure (CHF) [2, 3] and its implications in terms of increased hemodynamic burden to the failing heart. A pilot study using an angiotensin II (Ang II) receptor blocker, saralasin, in a short clinical experiment, demonstrated that Ang II blockade could successfully reverse the hemodynamic aberrations of decompensated CHF, while improving myocardial economy [4]. The decrease in myocardial oxygen consumption resulting from the fall in systemic vascular resistance was, paradoxically, accompanied by an increase in coronary blood flow, a fact that goes against the principles governing the regulation of coronary blood flow. This surprising observation was subsequently explained by the finding that the vasculature of vital organs (heart, kidney and brain) is particularly sensitive to the vasoconstrictive action of Ang II. Consequently, unlike other pharmacological vasodilators, RAS inhibition results in a preferential vasodilation of the coronary, renal and cerebral vasculature, thus maintaining or improving perfusion of vital organs, even in the face of falling systemic blood pressure [5, 6].

This is a preview of subscription content, 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   39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Gavras H, Brunner HR, Laragh JH, Sealey JE, Gavras I, Vukovich RA (1974) An angiotensin converting enzyme inhibitor to identify and treat vasoconstrictor and volume factors in hypertensive patients. N Engl J Med 291: 817–821

    Article  PubMed  CAS  Google Scholar 

  2. Genest J, Granger A, de Champlain J, Boucher R (1968) Endocrine factors in congestive heart failure. Amer J Cardiol 22: 35–42

    Article  PubMed  CAS  Google Scholar 

  3. Brown JJ, Davies DL, Johnson VW, Lever AF, Robertson JS (1970) Renin relationship in congestive heart failure, treated and untreated. Amer Heart J 80: 329–342

    Article  PubMed  CAS  Google Scholar 

  4. Gavras H, Flessas A, Ryan TJ, Brunner HR, Faxon DP, Gavras I (1977) Angiotensin II inhibition: treatment of congestive cardiac failure in a high-renin hypertension. J Amer Med Assn 238: 880–882, 1977

    Google Scholar 

  5. Liang C, Gavras H, Hood WBJr, (1978) Renin-angiotensin system inhibition in conscious sodium-depleted dogs: Effects on systemic and coronary hemodynamics. J Clin Invest 61: 874–883

    Article  PubMed  CAS  Google Scholar 

  6. Gavras H, Liang C, Brunner HR (1978) Redistribution of regional blood flow after inhibition of the angiotensin converting enzyme. Circ Res 43 (suppl I): I-59—I-63

    CAS  Google Scholar 

  7. Gavras H, Faxon DP, Berkoben J, Brunner HR, Ryan TJ (1978) Angiotensin converting enzyme inhibition in patients with congestive heart failure. Circulation 58: 770–775

    Article  PubMed  CAS  Google Scholar 

  8. Turini GA, Brunner HR, Ferguson RK, Rivier JL, Gavras H (1978) Congestive heart failure in normotensive man: hemodynamics, renin and angiotensin II blockade. Brit Heart J 40: 1134–1142

    Article  PubMed  CAS  Google Scholar 

  9. Turini GA, Brunner HR, Gribic M, Waeber B, Gavras H (1979) Improvement of chronic congestive heart failure by oral captopril. Lancet I: 1213–1215

    Article  Google Scholar 

  10. Faxon DP, Creager MA, Halperin JL, Gavras H, Coffman JD, Ryan TJ (1980) Central and peripheral hemodynamic effects of angiotensin Inhibition in patients with refractory congestive heart failure. Circulation 61: 925–931

    Article  PubMed  CAS  Google Scholar 

  11. Faxon DP, Creager MA, Halperin JL, Sussman HA, Gavras H, Ryan TJ (1982) The effect of angiotensin converting enzyme inhibition on coronary blood flow and hemodynamics in patients without coronary artery disease. Int J Cardiol 2: 251–262

    Article  PubMed  CAS  Google Scholar 

  12. Davis R, Ribner HS, Keung E, Sonnenblick EH, LeJemtel TH (1979) Treatment of chronic heart failure with captopril, an oral inhibitor of angiotensin-converting enzyme. N Engl J Med 301: 117–121

    Article  PubMed  CAS  Google Scholar 

  13. Levine TB, Franciosa JA, Cohn JA (1980) Acute and long-term response to an oral converting enzyme inhibitor, captopril, in congestive heart failure. Circulation 62: 35–41

    Article  PubMed  CAS  Google Scholar 

  14. Francis GS, Goldsmith SR, Levine B, Olivan MT, Cohn JN (1984) The neurohumoral axis in congestive heart failure. Ann Intern Med 101: 370–377

    PubMed  CAS  Google Scholar 

  15. Vantrimpont P, Rouleau JL, Ciampi A, Harel F, de Champlain J, the SAVE investigators (1998) Two-year time course and significance of neurohumoral activation in the SAVE study. Eur Heart J 19: 1552–1563

    CAS  Google Scholar 

  16. Gavras H (1994) Angiotensin-converting enzyme inhibition and the heart. Hypertension 23: 813–818

    Article  PubMed  CAS  Google Scholar 

  17. Lindpaintner K, Ganten D (1991) The cardiac renin-angiotensin system. Circ Res 68: 905–921

    Article  PubMed  CAS  Google Scholar 

  18. Dostal DEBaker KM (1995) Biochemistry, molecular biology, and potential roles of the cardiac renin—angiotensin system. In: NS Dhalla, N Takeda N, Nagano M (eds): The Failing Heart. Lippincott-Raven Publishers, Philadelphia, PA, 275–294

    Google Scholar 

  19. Kobayashi M, Furukawa Y, Chiba S (1978) Positive chronotropic and inotropic effects of angiotensin II in the dog heart. Eur J Pharmacol 50: 17–25

    Article  PubMed  CAS  Google Scholar 

  20. De Mello WC (1996) Renin-angiotensin system and cell communication in the failing heart. Hypertension 27: 1267–1272

    Article  PubMed  Google Scholar 

  21. Lee WB, Ismay MJLumbers ER (1980) Mechanisms by which angiotensin affects the heart rate of the conscious sheep. Circ Res 47: 286–292

    Article  PubMed  CAS  Google Scholar 

  22. Foult JM, Travalaro O, Autony I, Nittenberg A (1988) Direct myocardial and coronary effects of enalaprilat in patient with dilated cardiomyopathy; assessment by a bilateral intracoronary infusion technique. Circulation 77: 337–344

    Article  PubMed  CAS  Google Scholar 

  23. De Mello WC, Crespo MJ, Altieri PI (1992) Enalapril increases cardiac refractoriness. J Cardiovasc Pharmacol 20: 820–825

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  25. Wesseling H, De Graeff PA, Van Gilst WH, Kingma JH, De Langen CD ( 1989 Cardiac arrhythmias: a new indication for angiotensin-converting enzyme inhibitors? J Hum Hypertens 3 (suppl 1): 89–95

    PubMed  Google Scholar 

  26. Ponikowski P, Auker SD, Amadi A, Chua TP, Cerquetain D, Ondusova D, O’Sullivan C, Adamopoulos S, Piepoli MCoats AJS (1996) Heart rhythms, ventricular arrhythmias and death in chronic heart failure. J Cardiac Fail 2: 1772–1783

    Article  Google Scholar 

  27. Carlsson LAbrahamsson T (1989) Ramiprilat attenuates the local release of noradrenaline in the ischemic myocardium. Eur J Pharmacol 166: 157–164

    Article  PubMed  CAS  Google Scholar 

  28. Regoli D (1986) Kinins, receptors, antagonists. Adv Exp Med Biol 198: 549–558

    PubMed  Google Scholar 

  29. Carretero OA, Miyazaki S, Scicli AG (1981) Role of knins in the acute antihypertensive effect of the converting enzyme inhibitor captopril. Hypertension 3: 18–22

    Article  PubMed  CAS  Google Scholar 

  30. Benetos A, Gavras H, Stewart JM, Vavrek RJ, Hatinoglou S, Gavras I (1986) Vasodepressor role of endogenous bradykinin assessed by a bradykinin antagonist. Hypertension 8: 971–974

    Article  PubMed  CAS  Google Scholar 

  31. Bao G, Gohlke P, Qadri F, Unger T (1992) Chronic kinin receptor blockade attentuates the anti-hypertensive effect of ramipril. Hypertension 20: 74–79

    Article  PubMed  CAS  Google Scholar 

  32. Ruocco NAJr Bergelson BA, Yu T-K, Gavras I, Gavras H (1995) Augmentation of coronary blood flow by ACE: Role of angiotensin and bradykinin. Clin Exper Hypertens 17: 1059–1072

    Google Scholar 

  33. Fenoy FJ, Scicli AG, Carretero O, Roman RJ (1991) Effect of an angiotensin II and a kinin recep- tor antagonist on he renal hemodynamic response to captopril. Hypertension 17: 1038–1044

    Article  PubMed  CAS  Google Scholar 

  34. McGiff JC, Itkoviz HD, Terragno A, Wong PYK (1976) Modulation and mediation of the action of the renal kallikrein-system by prostaglandins. Fed Proc 35: 175–180

    PubMed  CAS  Google Scholar 

  35. Weimer G, Scholkens BA, Becker RHA, Busse R (1991) Ramiprilat enhances endothelial-autacoid formation by inhibiting breakdown of endothelium-derived bradykinin. Hypertension 18: 558–563

    Article  Google Scholar 

  36. Wang Y-X, Gavras I, Wierzba T, Lammek B, Gavras H (1992) Inhibition of nitric oxide, bradykinin, and prostaglandins in normal rats. Hypertension 19 (suppl II): 255–261

    Google Scholar 

  37. Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 43: 109–142

    PubMed  CAS  Google Scholar 

  38. Islim IF, Beevers DG, Bareford D (1992) The effect of antihypertensive drugs on in vivo platelet activity in essential hypertension. J Hypertension 10: 379–383

    Article  CAS  Google Scholar 

  39. Kohlman O Jr, De Assis Rocha Neves F, Ginoza M, Tavares A, Cezaretti ML, Zanella MT, Ribeiro AB, Gavras I, Gavras H (1995) Role of bradykinin in insulin sensitivity and blood pressure regulation during hyperinsulinemia. Hypertension 25: 1003–1007

    CAS  Google Scholar 

  40. Tomiyama H, Kushiro T, Abeta H, Islin T, Takahashi A, Furukawa I Asagami T, Hino T, Saito F, Otsuka Yet al (1994) Kinins contribute to the improvement of insulin sensitivity during treament with angiotensin converting enzyme inhibitor. Hypertension 23: 450–455

    Article  PubMed  CAS  Google Scholar 

  41. Li K, Chen X (1987) Protective effects of captopril and enalapril on myocardial ischemia and reperfusion damage of rat. J Mol Cell Cardiol 19: 909–915

    Article  PubMed  CAS  Google Scholar 

  42. Tio RA, De Langen CDJ, De Graeff PA, Van Gilst WH, Bel KJ, Wolters KGTP, Mook PH, van Wijngaarden J, Wesseling H (1990) The effects of oral pretreatment with zofenopril, an angiotensin-converting enzyme inhibitor, on early reperfusion and subsequent electrophysiologic stability in the pig. Cardiovasc Drug Therapy 4: 695–704

    Article  CAS  Google Scholar 

  43. Scholkens BA, Linz W, Konig W (1988) Effects of the angiotensin converting enzyme inhibitor ramipril in isolated ischemic rat heart are abolished by a bradykinin antagonist. J Hypertension 6 (suppl 4): 525–528

    Google Scholar 

  44. Gavras I (1992) Bradykinin-mediated effects of ACE inhibition. Kidney Int 42: 1020–1029

    Article  PubMed  CAS  Google Scholar 

  45. Staszewska-Barczak J, Van JR (1967) The release of catecholamines from the adrenal medulla by peptides. Brit J Pharmacol Chemother 30: 655–667

    CAS  Google Scholar 

  46. Rump LC, Berlit T, Schwertfeger E, Beyerdorf F, Schollmeyer P, Bohmann C (1997) Angiotensin converting enzyme inhibition unmasks the sympthofacilitatory effect of bradykinin in human right atrium. J Hypertension 15: 1263–1270

    Article  CAS  Google Scholar 

  47. Van Gilst WH, De Graeff PA, Wesseling H, de Langen CDJ (1986) Reduction of reperfusion arrhythmias in the ischemic isolated rat heart by angiotensin converting enzyme inhibitors: A comparison of captopril, enalapril, and HOE498. J Cardiovasc Pharmacol 8: 722–728

    PubMed  Google Scholar 

  48. Lee Y-M, Peng Y-Y, Ding Y-A, Yen M-H (1997) Losartan attenuates myocardial ischemia-induced ventricular arrhythmias and reperfusion injury in spontaneously hypertensive rats. Amer J Hypertens 10: 852–858

    Article  CAS  Google Scholar 

  49. Curtiss C, Cohn JN, Vrobel T, Franciosa JA (1978) Role of the renin-angiotensin system in the systemic vasoconstriction of chronic congestive heart failure. Circulation 58: 763–770

    Article  PubMed  CAS  Google Scholar 

  50. Dzau VJ, Colucci WS, Williams GH, Curfman G, Meggs L, Hollenberg NK (1980) Sustained effectiveness of converting enzyme inhibition in patients with severe congestive heart failure. N Engl J Med 302: 1373–1379

    Article  PubMed  CAS  Google Scholar 

  51. Pfeffer MA, Pfeffer JA, Steinberg C, Finn P (1985) Survival and experimental myocardial infarction: beneficial effects of long-term therapy with captopril. Circulation 72: 406–412

    Article  PubMed  CAS  Google Scholar 

  52. Sharpe N, Murphy J, Smith H, Hannan S (1988) Treatment of patients with symptomless left ventricular dysfunction after myocardial infarction. Lancet 1: 255–259

    Article  PubMed  CAS  Google Scholar 

  53. Pfeffer MA, Lamas GA, Vaughan DE, Paris AF, Braunwald E (1988) Effect of captopril on progressive ventricular dilation after anterior myocardial infarction. N Engl J Med 319: 80–86

    Article  PubMed  CAS  Google Scholar 

  54. Captopril Multicenter Research Group (1983) A placebo-controlled trial of captopril in refractory chronic congestive heart failure. JAmer Coll Cardiol 2: 755–763

    Article  Google Scholar 

  55. The CONSENSUSTria1 Study Group (1987) Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalpril Survival Study (CONSENSUS). N Engl J Med 316: 1429–1435

    Article  Google Scholar 

  56. Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ, Cuddy TE, Davis BR, Geltman EM, Goldman S, Flater GC et al (1992) Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the Survival and Ventricular Enlargement Trial. N Engl J Med 327: 669–677

    Article  PubMed  CAS  Google Scholar 

  57. The SOLVDInvestigators (1991) Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 325: 293–302

    Article  Google Scholar 

  58. The SOLVDInvestigators (1992) Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 327: 685–691

    Article  Google Scholar 

  59. Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, Tristawi F, Smith R, Dunkman B, Loeb H, Wong M et al (1991) A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic heart failure. N Engl J Med 325: 303–310

    Article  PubMed  CAS  Google Scholar 

  60. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators (1993) Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 342: 821–828

    Google Scholar 

  61. Hall AS, Murray GD, Ball SG on behalf of the AIREXStudy Investigators (1997) Follow-up study of patients randomly allocated ramipril or placebo for heart failure after acute myocardial infarction: AIRE Extension (AIREX) study. Lancet 349: 1493–1497

    CAS  Google Scholar 

  62. Ambrosioni E, Borghi C, Magnani B for the Survival of myocardial Infarction Long-term evaluation (SMILE) Study Investigators (1995) The effect of the angiotensin-converting enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. N Engl J Med 332: 80–85

    CAS  Google Scholar 

  63. GISSI-3 (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico) (1994) Effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6–week mortality and ventricular function after acute myocardial infarction. Lancet 343: 1115–1122

    Google Scholar 

  64. Kober L, Torp-Pedersen C, Carlsen JE, et al for the Trandolapril Cardiac Evaluation (TRACE) Study Group (1995) A clinical trial of the angiotensin-converting enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 333: 1670–1676

    Google Scholar 

  65. Garg R, Yusuf S (1995) Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. J Amer Med Assn 273: 1450–1456

    Article  CAS  Google Scholar 

  66. Texter M, Lees RS, Pitts B, Dinsmore RE, Uprichard AC (1993) The Quinapril Ischemic Event Trial (QUIET) design and methods; evaluation of chronic ACE inhibitor therapy after coronary artery intervention. Cardiovasc Drug Ther 7: 273–282

    Article  CAS  Google Scholar 

  67. ACE inhibitor Myocardial Infarction Collaborative Group (1998) Indication for ACE inhibitors in the early treatment of acute myocardial infarction: Systematic overview of individual data from 100,000 patients in randomized trials. Circulation 97: 2202–2212

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hypertension and Atherosclerosis Section, Department of Medicine, Boston University School of Medicine, Boston, MA, 02118, USA

    Irene Gavras & Haralambos Gavras

Authors
  1. Irene Gavras
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haralambos Gavras
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology, Institute of Pharmacology of Sherbrooke, Medical School, Sherbrooke University, J1H-5N4, Sherbrooke, PQ, Canada

    Pedro D’Orléans-Juste  & Gérard E. Plante  & 

  2. Departments of Medicine (Nephrology), Physiology and Pharmacology, Institute of Pharmacology, University of Sherbrooke, Sherbrooke, Québec, Canada

    Gérard E. Plante

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Birkhäuser Verlag/Switzerland

About this chapter

Cite this chapter

Gavras, I., Gavras, H. (2001). The role of ACE inhibition in heart failure. In: D’Orléans-Juste, P., Plante, G.E. (eds) ACE Inhibitors. Milestones in Drug Therapy MDT. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-7579-0_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-7579-0_6

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-7581-3

  • Online ISBN: 978-3-0348-7579-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation