Chronic heart failure as a state of reduced effectiveness of the natriuretic peptide system: implications for therapy

Eur J Heart Fail. 2017 Feb;19(2):167-176. doi: 10.1002/ejhf.656. Epub 2016 Oct 21.

Abstract

Natriuretic peptides (NPs) promote diuresis, natriuresis and vasodilation in early chronic heart failure (CHF), countering renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) overstimulation. Despite dramatic increases in circulating NP concentrations as CHF progresses, their effects become blunted. Increases in diuresis, natriuresis, and vasodilation after administration of exogenous atrial (ANP) or brain (BNP) natriuretic peptides are attenuated in patients with advanced CHF compared with controls. Several major factors may account for the reduced effectiveness of the natriuretic peptide system (NPS) in CHF. First, there is reduced availability of active forms of NPs, namely BNP. Second, target organ responsiveness becomes diminished. Third, the counter-regulatory hormones of the RAAS and SNS, and endothelin-1 become over-activated. Therefore, pharmacological approaches to enhance the functional effectiveness of the NPS in CHF have been explored in recent years. In terms of clinical outcomes, studies of synthetic BNP, or of neprilysin inhibitors alone or associated with an angiotensin converting enzyme inhibitor, have been controversial for several reasons. Recently, however, encouraging results have been obtained with the angiotensin receptor neprilysin inhibitor sacubitril/valsartan. The available data show that treatment with sacubitril/valsartan is associated with increased levels of NPs and their intracellular mediator cyclic guanosine monophosphate, suggesting improved functional effectiveness of the NPS, in addition to beneficial effects on mortality and morbidity outcomes. Therefore, combined targeting of the NPS and RAAS with sacubitril/valsartan emerges as the current optimal approach for redressing the neurohormonal imbalance in CHF.

Keywords: Atrial natriuretic peptide; Brain natriuretic peptide; Heart failure; Natriuretic peptide; Neprilysin.

Publication types

  • Review

MeSH terms

  • Aminobutyrates / therapeutic use
  • Angiotensin Receptor Antagonists / therapeutic use
  • Atrial Natriuretic Factor / metabolism*
  • Biphenyl Compounds
  • Chronic Disease
  • Drug Combinations
  • Endothelin-1 / metabolism*
  • Heart Failure / drug therapy
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology
  • Humans
  • Natriuretic Agents / therapeutic use
  • Natriuretic Peptide, Brain / metabolism*
  • Natriuretic Peptide, Brain / therapeutic use
  • Neprilysin / antagonists & inhibitors
  • Receptors, Atrial Natriuretic Factor / metabolism
  • Renin-Angiotensin System*
  • Sympathetic Nervous System / physiopathology
  • Tetrazoles / therapeutic use
  • Valsartan

Substances

  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Drug Combinations
  • Endothelin-1
  • Natriuretic Agents
  • Tetrazoles
  • Natriuretic Peptide, Brain
  • Valsartan
  • Atrial Natriuretic Factor
  • Neprilysin
  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor A
  • atrial natriuretic factor receptor B
  • atrial natriuretic factor receptor C
  • sacubitril and valsartan sodium hydrate drug combination