Skip to main content
SpringerLink
Log in

Inhibition of the Renin-Angiotensin-Aldosterone System

  • Chapter
  • First Online:
Heart Failure

  • 5111 Accesses

Abstract

In mild to severe heart failure, activation of the renin-angiotensin-aldosterone system is the primary abnormality. Increasing plasma levels of renin, angiotensin and aldosterone have direct effects on myocardium but also sodium and water handling, vascular contractility and reverse remodeling. Medical therapy to inhibit the renin-angiotensin-aldosterone system is the cornerstone of treatment for cardiomyopathy and heart failure.

This chapter will examine this neurohormonal pathway and discuss the deleterious effects when activated. Current medical therapy, aimed to block activation points along the pathway, will be reviewed.

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

Access this chapter

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 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover 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

Institutional subscriptions

References

  1. Schrier RW. Pathogenesis of sodium and water retention in high-output and low-output cardiac failure, nephrotic syndrome cirrhosis, and pregnancy. N Engl J Med. 1988;319:1065–72 1127-34.

    Article  CAS  PubMed  Google Scholar 

  2. Edwin K. Jackson. Goodman and gilman’s the pharmacological basis of therapeutics, 10th edn. McGraw Hill, New York; 2001, p. 809–21.

    Google Scholar 

  3. Hensen J, Abraham WT, Durr J, Shrier RW. Aldosterone in congestive heart failure: analysis of determinants and role in sodium retention. Am J Nephrol. 1991;11:441–6.

    Article  CAS  PubMed  Google Scholar 

  4. Rashid H. Direct renin inhibition: an evaluation of the safety and tolerability of aliskiren. Curr Med Res Opin. 2008;24:2627–37.

    Article  CAS  PubMed  Google Scholar 

  5. Jackson G, Gibbs CR, Davies MK, Lip GYH. Pathophysiology. Brit Med J. 2000;320:1676.

    Google Scholar 

  6. Dluhy RG, Williams GH. Aldosterone-villain or bystander? N Engl J Med. 2004;351:8–10.

    Article  CAS  PubMed  Google Scholar 

  7. Weber KT. Aldosterone in congestive heart failure. N Engl J Med. 2001;345:1689–97.

    Article  CAS  PubMed  Google Scholar 

  8. Mizuno Y, Yoshimura M, Yasue H, Sakamoto T, Ogawa H, Kugiyama K, et al. Aldosterone production is activated in failing ventricle in humans. Circulation. 2001;103:72–7.

    Article  CAS  PubMed  Google Scholar 

  9. Pitt B, Reichek N, Willenbrock R, Zannad F, Phillips RA, Roniker B, et al. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: The 4E-left ventricular hypertrophy study. Circulation. 2003;108:1831–8.

    Article  CAS  PubMed  Google Scholar 

  10. McEwan PE, Gray GA, Sherry L, Webb DJ, Kenyon CJ. Differential effects of angiotensin II on cardiac cell proliferation and intramyocardial perivascular fibrosis in vivo. Circulation. 1998;98:2765–73.

    Article  CAS  PubMed  Google Scholar 

  11. Captopril Multicenter Trial (Captopril Multicenter Research Group). A placebo controlled trial: captopril in refractory chronic congestive heart failure. J Am Coll Cardiol. 1983;2:755–63.

    Article  Google Scholar 

  12. Pilote L, Abrahamowicz M, Rodriguez E, Eisenberg MJ, Rahme E. Mortality rates in elderly patients who take different angiotensin-converting enzyme inhibitors after acute myocardial infarction: a class effect? Ann Intern Med. 2004;141:102–12.

    Article  PubMed  Google Scholar 

  13. Jorde UP, Ennezat PV, Lisker J, Suryadevara V, Infeld J, Cukon S, et al. Maximally recommended doses of angiotensin-converting enzyme (ACE) inhibitors do not completely prevent ACE-mediated formation of angiotensin II in chronic heart failure. Circulation. 2000;101:844–6.

    Article  CAS  PubMed  Google Scholar 

  14. Pitt B, Segal R, Martinez FA, Meurers G, Cowley AJ, Thomas I, et al. Randomized trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet. 1997;349:747–52.

    Article  CAS  PubMed  Google Scholar 

  15. Cohn JN, Tognoni G, for the Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;341:1675.

    Google Scholar 

  16. Granger CB, McMurray JJ, Yusuf S, Held P, Michelson EL, Olofsson B, Ostergren J, et al. CHARM Investigators and Committees.. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet. 2003;362:772–6.

    Article  CAS  PubMed  Google Scholar 

  17. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, 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;341:709–17.

    Article  CAS  PubMed  Google Scholar 

  18. The Consensus Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (Consensus). N Engl J Med. 1987;316:1429–35.

    Article  Google Scholar 

  19. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325:293–302.

    Article  Google Scholar 

  20. The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med. 1992;327:685–91.

    Article  Google Scholar 

  21. Carson P, Ziesche S, Johnson G, Cohn JN. Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. J Card Fail. 1999;5:178–87.

    Article  CAS  PubMed  Google Scholar 

  22. Pitt B, Poole-Wilson PA, Segal R, Martinez FA, Dickstein K, Camm AJ, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomized trial—the Losartan Heart Failure Survival Study, ELITE II. Lancet. 2000;355:1582–7.

    Article  CAS  PubMed  Google Scholar 

  23. McMurray JJ, Ostergren J, Swedberg K, Granger CB, Held P, Michelson EL, et al. CHARM Investigators and Committees.Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic dysfunction taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet. 2003;362:767–71.

    Article  CAS  PubMed  Google Scholar 

  24. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eperenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309–21.

    Article  CAS  PubMed  Google Scholar 

  25. McMurray JJ, Packer M, Desai A, et al. Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure. N Engl J Med. 2014;371:993–1004.

    Article  PubMed  Google Scholar 

  26. Yancy, Clyde et al 2016 ACC/AHA?HFSA focused update on new pharmacological therapy for hearty failure: an update on new pharmacological therapy for heart failure: an update of the 2013 ACCF/AHA/guideline for the management of heart failure. Circulation. 2016; 134.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Director Heart Transplant and Ventricular Assist Devices, University of Maryland Division of Cardiology, 110 South Paca Street, Baltimore, MD, 21201, USA

    Erika D. Feller MD (Assistant Professor)

Authors
  1. Erika D. Feller MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erika D. Feller MD .

Editor information

Editors and Affiliations

  1. Division of Cardiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Howard Eisen

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer-Verlag London

About this chapter

Cite this chapter

Feller, E.D. (2017). Inhibition of the Renin-Angiotensin-Aldosterone System. In: Eisen, H. (eds) Heart Failure. Springer, London. https://doi.org/10.1007/978-1-4471-4219-5_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-4219-5_5

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-4218-8

  • Online ISBN: 978-1-4471-4219-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation