Natriuretic Peptide Mechanisms in Heart Failure Management

Natruiretic peptides are a family of cardiac hormones, principally atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), that are released in response to myocardial wall stress. Binding to particulate guanylate cyclase receptors (notably NPR-A) leads to intracellular cyclic guanosine monophosphate (cGMP) accumulation, promoting vasodilation, natriuresis and inhibition of maladaptive neurohormonal pathways such as the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system. In clinical practice, measurements of BNP or its inactive fragment NT-proBNP serve as biomarkers for diagnosis, risk stratification and monitoring of therapeutic efficacy. Therapeutic strategies to augment natriuretic peptide signalling include recombinant peptides (for example nesiritide), neprilysin inhibition and combined angiotensin receptor-neprilysin inhibitor (ARNI) therapy. Such interventions rebalance neuroendocrine dysregulation, reduce cardiac remodelling and improve clinical outcomes. Emerging approaches aim to enhance peptide stability, receptor selectivity and targeted delivery to achieve long-term cardiovascular protection worldwide.

Research from Nature Portfolio

Recent structural equation modelling of intracoronary pressure measurements has revealed that plasma BNP levels respond sensitively to discrete changes in coronary ischaemia, quantified by the baseline distal-to-aortic pressure ratio and fractional flow reserve. The study further demonstrated that BNP elevation contributes to coronary vasodilation, supporting a direct cardioprotective feedback loop. Path-modelling analyses examining left ventricular cavity volumes have clarified opposing roles of end-systolic and end-diastolic volume in determining cardiac overload and BNP secretion, underscoring the prognostic value of volumetric indices. In populations with extremely low BNP concentrations, an inverse association with cardiac troponin I suggests that insufficient BNP may permit subclinical myocardial injury, highlighting the importance of maintaining minimal peptide thresholds for cardioprotection.

Natriuretic Peptide Mechanisms in Heart Failure Management publication trend

The graph below shows the total number of articles in natriuretic peptide mechanisms in heart failure management across all publications each year (not limited to Nature Index journals).

Technical terms

Natruiretic peptides: Hormones released by the heart that induce vasodilation and natriuresis.

Neprilysin: Metalloprotease enzyme responsible for degrading natriuretic peptides.

ARNI: Combined angiotensin receptor-neprilysin inhibitor that enhances natriuretic peptide bioactivity.

NPR-A: Particulate guanylate cyclase receptor that mediates the effects of ANP and BNP.

cGMP: Cyclic guanosine monophosphate, second messenger generated by NPR-A activation.

Fractional flow reserve (FFR): Ratio of distal coronary pressure to aortic pressure under hyperaemia, indicating stenosis severity.

Left ventricular end-systolic volume index (LVESVI): Normalised measure of residual ventricular volume after contraction, reflecting remodelling.

References

1. Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure. Journal of Biological Engineering (2018).
2. BNP and NT-proBNP as Diagnostic Biomarkers for Cardiac Dysfunction in Both Clinical and Forensic Medicine. International Journal of Molecular Sciences (2019).
3. Drug therapy for patients with systolic heart failure after the PARADIGM-HF trial: in need of a new paradigm of LCZ696 implementation in clinical practice. BMC Medicine (2015).
4. A Highly-sensitized Response of B-type Natriuretic Peptide to Cardiac Ischaemia Quantified by Intracoronary Pressure Measurements. Scientific Reports (2020).
5. Associations between Left Ventricular Cavity Size and Cardiac Function and Overload Determined by Natriuretic Peptide Levels and a Covariance Structure Analysis. Scientific Reports (2017).
6. Increased Levels of Cardiac Troponin I in Subjects with Extremely Low B-type Natriuretic Peptide Levels. Scientific Reports (2018).
7. Neurohumoral Activation in Heart Failure. International Journal of Molecular Sciences (2023).
8. Atrial Natriuretic Peptides as a Bridge between Atrial Fibrillation, Heart Failure, and Amyloidosis of the Atria. International Journal of Molecular Sciences (2023).
9. Increasing heart vascularisation after myocardial infarction using brain natriuretic peptide stimulation of endothelial and WT1+ epicardial cells. eLife (2020).