Natriuretic Peptide: Physiology and What Research Reports
Natriuretic peptides are a family of hormones — chiefly ANP, BNP and CNP — released mainly by heart muscle and vascular tissue in response to stretch and other signals. They act on membrane receptor guanylyl cyclases to promote sodium and water excretion, vasodilation and antifibrotic signalling. Blood levels of BNP and NT-proBNP are widely used as heart-failure markers. This page summarises what the cited literature reports about their production, receptors, measurement and research uses.
Definition: what the term covers
The phrase natriuretic peptide refers to a small family of structurally related peptide hormones built around a 17-amino-acid ring closed by a disulfide bond. The three best-characterised members are atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). "Natriuretic" describes the original observed action — increased urinary sodium excretion — but reviews of the system describe a much broader signalling role spanning blood pressure regulation, fluid balance, cardiac remodelling and vascular tone (PMID 33894277).
This page is for educational purposes only and is not medical advice; consult a licensed physician for any question about a medical condition, test result or treatment.
Where natriuretic peptides are produced
ANP is stored in granules within atrial cardiomyocytes and released when the atrial wall is stretched, as reviewed in an overview of atrial natriuretic peptide physiology (PMID 32965928). BNP is produced predominantly by ventricular myocardium and, in the natriuretic peptide system reviewed in heart failure, its precursor is cleaved into the active hormone and the inactive N-terminal fragment NT-proBNP (PMID 33894277). CNP is more characteristically endothelial and vascular; a translational review examined CNP specifically in the context of essential hypertension and described its signalling in the vascular wall (PMID 37325397).
Secretion is not simply passive. One study reported that zDHHC9 regulated cardiomyocyte Rab3a activity and atrial natriuretic peptide secretion through palmitoylation of Rab3gap1, identifying a lipid-modification step in the release pathway (PMID 37325411). Morphological work in experimental hypertension examined the synthesis and excretion of atrial natriuretic peptide in secretory cardiomyocytes, reporting changes in the secretory apparatus under pressure load (PMID 32651808).
What they do: receptors and downstream signalling
Natriuretic peptides act through cell-surface receptors. NPR-A and NPR-B are receptor guanylyl cyclases that generate cyclic GMP; NPR-C is generally described as a clearance and signalling receptor. Researchers built epitope-tagged and phosphomimetic mouse models specifically to investigate natriuretic peptide-stimulated receptor guanylyl cyclases, and reported that receptor phosphorylation state was central to how the receptors responded to their ligands (PMID 36340689).
NPR-C has attracted attention beyond clearance. In mice, one study reported that natriuretic peptide receptor-C protected against angiotensin II-mediated sinoatrial node disease, linking the receptor to electrical function in the heart's pacemaker region (PMID 30623142/). Tool compounds support this work: chemists published a modified synthesis of the peptidomimetic natriuretic peptide receptor-C antagonist M372049, a reagent used to probe NPR-C pharmacology (PMID 32153307).
| Member | Principal source described | Receptor emphasis in cited literature |
|---|---|---|
| ANP | Atrial cardiomyocyte granules, released on stretch (PMID 32965928) | NPR-A guanylyl cyclase signalling (PMID 36340689) |
| BNP / NT-proBNP | Ventricular myocardium; precursor cleaved to active and inactive fragments (PMID 33894277) | NPR-A, with clearance via NPR-C and peptidases (PMID 33894277) |
| CNP | Endothelium and vascular wall (PMID 37325397) | NPR-B and NPR-C (PMID 37325397) |
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Try it freeHow natriuretic peptides are measured and studied
In clinical research the dominant approach is plasma immunoassay of BNP or NT-proBNP. A review of the natriuretic peptide system in heart failure described both the diagnostic use of these circulating markers and the therapeutic implications of manipulating the pathway, including the rationale for blocking peptide degradation (PMID 33894277). Measurement is not limited to adult cardiology: one study reported that plasma natriuretic peptide levels reflected the status of heart failure in fetuses with arrhythmia, using circulating peptide as a readout of fetal cardiac load (PMID 31414622).
Beyond cardiology, researchers have evaluated natriuretic peptides as tissue biomarkers. A biomarker study examined C-type natriuretic peptide and its precursor as potential markers in human prostate cancer (PMID 25808436).
Laboratory and mechanistic methods
- Genetic mouse models — epitope-tagged and phosphomimetic receptor knock-in mice were generated to study natriuretic peptide-stimulated guanylyl cyclase receptors (PMID 36340689).
- Disease models — angiotensin II infusion models were used to test whether NPR-C influenced sinoatrial node disease in mice (PMID 30623142/).
- Histology of secretory cells — cardiomyocyte secretory granules were examined in experimental hypertension to track ANP synthesis and release (PMID 32651808).
- Chemical tools — synthetic routes to the NPR-C antagonist M372049 were reported to support receptor pharmacology (PMID 32153307).
- Gene-expression profiling — natriuretic peptide B expression was measured in a sensory-neuroscience context (PMID 40705694).
Why the term appears outside cardiology
Two cited lines of work illustrate how far the family reaches. In sensory biology, a 2025 study reported upregulated natriuretic peptide B expression as a hallmark of chronic itch, positioning the peptide within itch-signalling circuitry rather than cardiovascular control (PMID 40705694). In endocrinology, a study in healthy men examined atrial natriuretic peptide and leptin interactions, probing crosstalk between a cardiac hormone and an adipose-derived signal (PMID 37455918).
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Get the appRelevance to peptide research literacy
Readers who encounter "natriuretic peptide" typically meet it in one of three ways: as a blood test (BNP or NT-proBNP), as a hormone described in cardiovascular physiology, or as a research target in receptor pharmacology. The cited reviews treat the system as a counter-regulatory axis to pressure and volume overload, and discuss therapeutic strategies aimed at the pathway rather than at any single peptide molecule (PMID 33894277, PMID 37325397).
Safety and tolerability: What Studies Report
The verified papers summarised here were primarily physiological, mechanistic, diagnostic and biomarker studies; they did not provide a tolerability or adverse-event profile for administered natriuretic peptides in humans, and no dosing schedule is described in their reported scope. The heart-failure review discussed diagnostic and therapeutic implications of the natriuretic peptide system at the level of pathway strategy (PMID 33894277). Questions about approved medicines that act on this pathway belong with a licensed physician.
Key takeaways
- ANP, BNP and CNP form a hormone family acting through guanylyl cyclase receptors (PMID 36340689).
- ANP release from atrial cardiomyocytes is granule-based and regulated (PMID 37325411).
- Circulating BNP and NT-proBNP are used as heart-failure markers, as described in a pathway review (PMID 33894277).
- The family also appears in itch neuroscience and in cancer biomarker work (PMID 40705694, PMID 25808436).
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Start learning freeReferences
- The natriuretic peptide system in heart failure: Diagnostic and therapeutic implications (Pharmacology & Therapeutics, 2021)
- Atrial Natriuretic Peptide (2026)
- Upregulated natriuretic peptide B expression as a hallmark of chronic itch (Pain, 2025)
- Atrial natriuretic peptide and leptin interactions in healthy men (Frontiers in Endocrinology, 2023)
- Epitope-tagged and phosphomimetic mouse models for investigating natriuretic peptide-stimulated receptor guanylyl cyclases (Frontiers in Molecular Neuroscience, 2022)
- C-Type Natriuretic Peptide in Essential Hypertension: Old Ways for a New Time (JACC: Basic to Translational Science, 2023)
- zDHHC9 Regulates Cardiomyocyte Rab3a Activity and Atrial Natriuretic Peptide Secretion Through Palmitoylation of Rab3gap1 (JACC: Basic to Translational Science, 2023)
- Natriuretic Peptide Receptor-C Protects Against Angiotensin II-Mediated Sinoatrial Node Disease in Mice (JACC: Basic to Translational Science, 2018)
- Modified Synthesis of the Peptidomimetic Natriuretic Peptide Receptor-C Antagonist M372049 (Tetrahedron Letters, 2020)
- Synthesis and Excretion of Atrial Natriuretic Peptide in Secretory Cardiomyocytes in Experimental Hypertension (Bulletin of Experimental Biology and Medicine, 2020)
- Plasma natriuretic peptide levels reflect the status of the heart failure in fetuses with arrhythmia (The Journal of Maternal-Fetal & Neonatal Medicine, 2021)
- C-type natriuretic peptide and its precursor: potential markers in human prostate cancer (Biomarkers in Medicine, 2015)
Frequently asked questions
What is a natriuretic peptide?▾
It is a member of a family of peptide hormones — mainly ANP, BNP and CNP — that share a disulfide-closed ring structure and signal through guanylyl cyclase receptors. A review of the natriuretic peptide system in heart failure described their roles in sodium and volume handling, vascular tone and cardiac remodelling (PMID 33894277), with receptor signalling detailed in mouse model work (PMID 36340689).
Where are ANP, BNP and CNP made?▾
An overview of atrial natriuretic peptide described ANP as stored in atrial cardiomyocyte granules and released on stretch (PMID 32965928). A heart-failure review described BNP as predominantly ventricular, with its precursor cleaved into active hormone and NT-proBNP (PMID 33894277). A translational review discussed CNP in the vascular wall in essential hypertension (PMID 37325397).
How is natriuretic peptide measured in research?▾
Most clinical work measures circulating BNP or NT-proBNP by immunoassay. A review outlined the diagnostic use of these markers in heart failure (PMID 33894277). One study reported that plasma natriuretic peptide levels reflected heart failure status in fetuses with arrhythmia (PMID 31414622). Tissue-level work has also examined CNP and its precursor as biomarkers (PMID 25808436).
What receptors do natriuretic peptides use?▾
Researchers describe NPR-A and NPR-B as receptor guanylyl cyclases producing cyclic GMP, and NPR-C as a clearance and signalling receptor. Epitope-tagged and phosphomimetic mouse models were generated to study these receptors and reported that phosphorylation state shaped responses (PMID 36340689). An NPR-C antagonist, M372049, has a published synthesis used as a research tool (PMID 32153307).
Is natriuretic peptide relevant outside the heart?▾
Yes. A 2025 study reported upregulated natriuretic peptide B expression as a hallmark of chronic itch, placing the peptide in sensory signalling (PMID 40705694). A study in healthy men examined atrial natriuretic peptide and leptin interactions (PMID 37455918), and a biomarker study assessed C-type natriuretic peptide and its precursor in human prostate cancer (PMID 25808436).
Do the cited papers describe dosing of natriuretic peptides?▾
No. The verified papers summarised here were physiological, mechanistic, diagnostic or biomarker studies and did not report human dosing schedules within their described scope. The heart-failure review discussed therapeutic implications of the pathway at a strategy level rather than as a protocol (PMID 33894277). This information is educational only and is not medical advice.
What did animal studies report about NPR-C?▾
One mouse study reported that natriuretic peptide receptor-C protected against angiotensin II-mediated sinoatrial node disease, linking the receptor to pacemaker function (PMID 30623142). Separately, researchers reported that zDHHC9 regulated cardiomyocyte Rab3a activity and atrial natriuretic peptide secretion through palmitoylation of Rab3gap1 (PMID 37325411). These were preclinical findings, not human outcomes.
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References
This page summarises published research for education — it is not medical advice, and nothing here is a recommendation to use, purchase, or dose any substance. Study parameters described are what researchers reported, not instructions. Consult a qualified clinician before any health decision.