Pathophysiology of congestive heart failure: Role of atrial natriuretic factor and therapeutic implications

M. A. Perrella, K. B. Margulies, John C Jr. Burnett

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Endogenous atrial natriuretic factor (ANF) serves a functional role to maintain sodium homeostasis and inhibit activation of the renin-angiotensin-aldosterone system in acute congestive heart failure despite arterial hypotension. However, as heart failure progresses, maximal synthesis and release of ANF from both the atrial and ventricular myocardium may occur resulting in relative ANF deficiency. This relative deficiency of ANF results in a progressive inability to excrete sodium and antagonize the renin-angiotensin-aldosterone system. Consequently, agents that increase circulating ANF and (or) enhance its local action have potential therapeutic efficacy. Recent studies suggest that inhibitors of neutral endopeptidase 24.11, which block ANF degradation, potentiate the natriuretic action of endogenous ANF independent of systemic or renal hemodynamics. This action does not parallel increases in plasma ANF and is associated with marked increases in urinary ANF and cyclic guanosine monophosphate consistent with enhanced local action of the peptide. In addition, agents that selectively bind to biologically inactive ANF clearance receptors increase endogenous plasma ANF and promote increases in renal sodium excretion. These studies suggest a therapeutic role for neutral endopeptidase inhibition and clearance receptor blockade, while advancing our understanding of the pathophysiology of ANF in congestive heart failure.

Original languageEnglish (US)
Pages (from-to)1576-1581
Number of pages6
JournalCanadian Journal of Physiology and Pharmacology
Volume69
Issue number10
StatePublished - 1991

Fingerprint

Atrial Natriuretic Factor
Heart Failure
Therapeutics
Neprilysin
Sodium
Renin-Angiotensin System
Atrial Natriuretic Factor Receptors
Cyclic GMP
Hypotension
Action Potentials
Myocardium
Homeostasis
Hemodynamics
Kidney
Peptides

Keywords

  • atrial natriuretic factor
  • congestive heart failure
  • cyclic guanosine monophosphate
  • natriuresis
  • renin-angiotensin-aldosterone system

ASJC Scopus subject areas

  • Physiology
  • Pharmacology

Cite this

Pathophysiology of congestive heart failure : Role of atrial natriuretic factor and therapeutic implications. / Perrella, M. A.; Margulies, K. B.; Burnett, John C Jr.

In: Canadian Journal of Physiology and Pharmacology, Vol. 69, No. 10, 1991, p. 1576-1581.

Research output: Contribution to journalArticle

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