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Pathophysiologic role of the renin-angiotensin-aldosterone and sympathetic nervous systems in heart failure.
Am J Health Syst Pharm 2004; 61 Suppl 2:S4-13AJ

Abstract

PURPOSE

The pathophysiology of heart failure is reviewed, with particular focus on the role of abnormal neurohormonal activation of the sympathetic nervous system and the renin-angiotensin-aldosterone axis in the pathophysiology of this syndrome.

SUMMARY

Events preceding myocardial infarction and heart failure are driven in part by norepinephrine, angiotensin II, and aldosterone. The sympathetic nervous system likely evolved to mediate acute regulation of the cardiovascular system, not the sustained activation that is seen in heart failure. Overexpression of beta1-receptors in animal models results in decreased left ventricular ejection fraction and ventricular remodeling. In patients with systolic dysfunction, beta-blockade has improved left ventricular function and decreased the risk of sudden death. Chronic exposure to excess angiotensin II produces eccentric ventricular hypertrophy, vasoconstriction, and sodium retention. Angiotensin-converting enzyme (ACE) inhibition causes only a transient depression of aldosterone concentrations; the chronic benefit from ACE inhibition in patients with heart failure likely results from augmentation of bradykinin and not from the inhibition of angiotensin II production. Administration of eplerenone, a selective mineralocorticoid receptor antagonist, following induction of ischemic injury in animals, blocked the progressive ventricular dilatation and reduction in systolic function observed in control animals; clinical studies indicate that those findings can be translated to human cardiovascular disease. Overactivity of the mineralocorticoid receptor in cardiomyocytes could be important even in the absence of excessive levels of aldosterone. Clinical studies demonstrated that strategies of neurohormonal blockade using an ACE inhibitor, angiotensin II receptor antagonist, and beta-blocker are ineffective in reducing circulating aldosterone in patients with heart failure caused by left ventricular systolic dysfunction.

CONCLUSION

Aldosterone is a key deleterious hormone influencing all forms of cardiovascular disease, including hypertension, myocardial infarction, and heart failure. Treatment of many cardiovascular diseases should include specific antagonism of the adverse pathophysiologic consequences of aldosterone.

Authors+Show Affiliations

Division of Cardiology, Heart Failure Program, School of Medicine, University of North Carolina, 6110 Falconbridge Road, Suite 101, Chapel Hill, NC 27517, USA. kfa@med.unc.edu

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

15160833

Citation

Adams, Kirkwood F.. "Pathophysiologic Role of the Renin-angiotensin-aldosterone and Sympathetic Nervous Systems in Heart Failure." American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists, vol. 61 Suppl 2, 2004, pp. S4-13.
Adams KF. Pathophysiologic role of the renin-angiotensin-aldosterone and sympathetic nervous systems in heart failure. Am J Health Syst Pharm. 2004;61 Suppl 2:S4-13.
Adams, K. F. (2004). Pathophysiologic role of the renin-angiotensin-aldosterone and sympathetic nervous systems in heart failure. American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists, 61 Suppl 2, pp. S4-13.
Adams KF. Pathophysiologic Role of the Renin-angiotensin-aldosterone and Sympathetic Nervous Systems in Heart Failure. Am J Health Syst Pharm. 2004 May 1;61 Suppl 2:S4-13. PubMed PMID: 15160833.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pathophysiologic role of the renin-angiotensin-aldosterone and sympathetic nervous systems in heart failure. A1 - Adams,Kirkwood F,Jr PY - 2004/5/27/pubmed PY - 2004/8/11/medline PY - 2004/5/27/entrez SP - S4 EP - 13 JF - American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists JO - Am J Health Syst Pharm VL - 61 Suppl 2 N2 - PURPOSE: The pathophysiology of heart failure is reviewed, with particular focus on the role of abnormal neurohormonal activation of the sympathetic nervous system and the renin-angiotensin-aldosterone axis in the pathophysiology of this syndrome. SUMMARY: Events preceding myocardial infarction and heart failure are driven in part by norepinephrine, angiotensin II, and aldosterone. The sympathetic nervous system likely evolved to mediate acute regulation of the cardiovascular system, not the sustained activation that is seen in heart failure. Overexpression of beta1-receptors in animal models results in decreased left ventricular ejection fraction and ventricular remodeling. In patients with systolic dysfunction, beta-blockade has improved left ventricular function and decreased the risk of sudden death. Chronic exposure to excess angiotensin II produces eccentric ventricular hypertrophy, vasoconstriction, and sodium retention. Angiotensin-converting enzyme (ACE) inhibition causes only a transient depression of aldosterone concentrations; the chronic benefit from ACE inhibition in patients with heart failure likely results from augmentation of bradykinin and not from the inhibition of angiotensin II production. Administration of eplerenone, a selective mineralocorticoid receptor antagonist, following induction of ischemic injury in animals, blocked the progressive ventricular dilatation and reduction in systolic function observed in control animals; clinical studies indicate that those findings can be translated to human cardiovascular disease. Overactivity of the mineralocorticoid receptor in cardiomyocytes could be important even in the absence of excessive levels of aldosterone. Clinical studies demonstrated that strategies of neurohormonal blockade using an ACE inhibitor, angiotensin II receptor antagonist, and beta-blocker are ineffective in reducing circulating aldosterone in patients with heart failure caused by left ventricular systolic dysfunction. CONCLUSION: Aldosterone is a key deleterious hormone influencing all forms of cardiovascular disease, including hypertension, myocardial infarction, and heart failure. Treatment of many cardiovascular diseases should include specific antagonism of the adverse pathophysiologic consequences of aldosterone. SN - 1079-2082 UR - https://www.unboundmedicine.com/medline/citation/15160833/Pathophysiologic_role_of_the_renin_angiotensin_aldosterone_and_sympathetic_nervous_systems_in_heart_failure_ L2 - https://academic.oup.com/ajhp/article-lookup/doi/10.1093/ajhp/61.suppl_2.S4 DB - PRIME DP - Unbound Medicine ER -