Natriuretic Peptide Signaling in Cardiovascular Health

Natriuretic peptides constitute a family of structurally related hormones crucial to the regulation of blood volume, vascular tone and cardiac remodelling. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are principally released by atrial and ventricular myocytes in response to stretch, promoting natriuresis, diuresis and vasodilatation through activation of particulate guanylyl cyclase-A. C-type natriuretic peptide (CNP), largely of endothelial origin, engages guanylyl cyclase-B to modulate vascular homeostasis and paracrine regulation of smooth muscle and endothelial cell function. Clearance of all three peptides occurs in part via the natriuretic peptide receptor-C, which also mediates G-protein-coupled signalling. By elevating intracellular cyclic guanosine monophosphate (cGMP), natriuretic peptides counterbalance the renin–angiotensin–aldosterone system, inhibit fibrosis and hypertrophy, and limit inflammatory and proliferative responses in the vessel wall. Dysregulation of this axis contributes to hypertension, heart failure, atherosclerosis and vascular remodelling, while therapeutic augmentation of peptide levels or receptor activation offers promise for disease modification.

Research from Nature Portfolio

Single-cell transcriptomic and functional profiling of vascular smooth muscle cells in murine atherosclerotic lesions has revealed a dynamic shift from ANP/GC-A to CNP/GC-B signalling during phenotypic modulation. This transition marks the emergence of chondrocyte-like plaque cells, and targeted silencing of the CNP/GC-B axis accelerates this deleterious conversion. Conversely, preservation of CNP/GC-B activity limits maladaptive remodelling, underscoring its role as both marker and regulator of atheroprotective smooth muscle phenotypes. These findings illuminate the plasticity of cGMP signalling pathways and identify CNP/GC-B as a potential target to stabilise vascular lesions and attenuate progression of atherosclerosis.

Natriuretic Peptide Signaling in Cardiovascular Health publication trend

The graph below shows the total number of articles in natriuretic peptide signaling in cardiovascular health across all publications each year (not limited to Nature Index journals).

Technical terms

Atrial natriuretic peptide (ANP): A cardiac hormone secreted by atrial myocytes in response to stretch, which elicits natriuresis and vasodilatation via guanylyl cyclase-A.

B-type natriuretic peptide (BNP): A ventricular hormone released under conditions of pressure or volume overload, functioning similarly to ANP and serving as a biomarker of heart failure.

C-type natriuretic peptide (CNP): An endothelium-derived paracrine mediator that engages guanylyl cyclase-B to regulate vascular tone and cell proliferation.

Guanylyl cyclase-A (GC-A/NPR-A): A membrane-bound receptor that, upon binding ANP or BNP, catalyses the formation of cyclic guanosine monophosphate (cGMP).

Guanylyl cyclase-B (GC-B/NPR-B): A receptor activated by CNP to generate cGMP, primarily involved in paracrine regulation of vascular and skeletal tissues.

Natriuretic peptide receptor-C (NPR-C): A clearance receptor for natriuretic peptides that also couples to G-protein signalling pathways influencing vascular function.

Cyclic guanosine monophosphate (cGMP): A second messenger produced by guanylyl cyclase receptors that mediates vasodilatation, antiproliferative and antifibrotic effects.

Phenotypic modulation: The process by which vascular smooth muscle cells switch from a contractile state to a synthetic or chondrocyte-like phenotype during vascular disease.

References

1. NPRC deletion mitigated atherosclerosis by inhibiting oxidative stress, inflammation and apoptosis in ApoE knockout mice. Signal Transduction and Targeted Therapy (2023).
2. Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis. Nature Communications (2025).
3. Atrial and brain natriuretic peptides: Hormones secreted from the heart. Peptides (2018).
4. Endothelial C-type natriuretic peptide maintains vascular homeostasis. Journal of Clinical Investigation (2014).
5. The natriuretic peptide system in heart failure: Diagnostic and therapeutic implications. Pharmacology & Therapeutics (2021).