title: Pathophysiology of congestive heart failure: role of atrial natriuretic factor and therapeutic implications.
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.
authors.affiliation: Department of Cardiovascular, Mayo Clinic and Foundation, Rochester, MN 55905.
authors.forename: M A
authors.initials: MA
authors.lastname: Perrella
authors.forename: K B
authors.initials: KB
authors.lastname: Margulies
authors.forename: J C
authors.initials: JC
authors.lastname: Burnett
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans
chemical_list: D009320:Atrial Natriuretic Factor