ANP and BNP

ANP — atrial natriuretic peptide, atrial natriuretic factor (ANF), atriopeptin, cardionatrin; carperitide (recombinant ANP, Japan). BNP — B-type / brain natriuretic peptide; nesiritide (recombinant BNP, #137). Related: CNP (C-type natriuretic peptide), NT-proBNP (the inactive fragment measured in blood tests), vosoritide (CNP analogue)

Cardiovascular & circulation

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Summary

Class: Naturally occurring cardiac hormones. ANP is a 28-amino-acid peptide released from the atria; BNP is a 32-amino-acid peptide released mainly from the ventricles. Both have a 17-residue ring closed by a disulfide bond
Mechanism: Released when the heart is stretched by too much blood volume or pressure; act on the kidney to excrete sodium and water, relax blood vessels, and switch off the renin–angiotensin–aldosterone and sympathetic systems — the heart's own "pressure-relief valve"
Routes studied: Intravenous infusion (research and the two approved recombinant products); no oral form (peptides are destroyed in the gut). Neprilysin inhibitors (sacubitril) raise endogenous levels orally
Half-life: ANP ~2–5 minutes; BNP ~20 minutes; NT-proBNP ~1–2 hours (which is why it is the preferred blood test)
Storage: Hospital products: lyophilised vials, reconstituted before infusion. Research reagents only otherwise
Regulatory status: Native hormones not marketed as such. Carperitide approved in Japan only; nesiritide approved in the US (rarely used, see #137); sacubitril/valsartan (Entresto) approved widely

Doses are as reported in studies or by the community — never recommendations.

1What it is

In 1981 Adolfo de Bold injected extracts of rat atrial tissue into other rats and saw a dramatic increase in urine sodium and volume. The active substance, atrial natriuretic peptide, made the heart an endocrine organ for the first time. BNP followed in 1988, isolated from pig brain (hence the misleading name) but actually made mostly by the heart's ventricles. A third member, CNP, comes from blood-vessel lining and cartilage and is the basis of vosoritide for achondroplasia.

ANP and BNP are stored in granules in heart muscle cells and released when the chambers are stretched. ANP comes out quickly from the atria in response to moment-to-moment volume changes; BNP is produced mainly by ventricular muscle under sustained strain, so its level in blood tracks how hard the ventricles are working. That is why BNP and its inactive by-product NT-proBNP became the standard blood tests for heart failure: a stretched, failing ventricle pours them out.

As medicines the hormones have had a mixed career. Recombinant ANP (carperitide) has been used in Japan since 1995 for acute heart failure but never gained approval elsewhere. Recombinant BNP (nesiritide, #137) was approved in the US in 2001 and effectively abandoned after the 7,141-patient ASCEND-HF trial found it neither helped nor harmed. The successful strategy turned out to be indirect: stopping the enzyme neprilysin from breaking down the body's own natriuretic peptides, which is what sacubitril does in the combination drug sacubitril/valsartan. Community/self-directed use of ANP or BNP: essentially none documented; they are hospital infusions with of minutes.

2How it's thought to work

Receptors. ANP and BNP bind natriuretic peptide receptor-A (NPR-A, also called GC-A), a membrane guanylyl cyclase that raises intracellular cyclic GMP. CNP acts on NPR-B. A third receptor, NPR-C, has no signalling domain and mainly clears peptides from the blood.

Kidney. cGMP in the collecting duct and glomerulus increases sodium and water excretion, raises filtration pressure and reduces renin release.

Blood vessels. smooth-muscle relaxation lowers blood pressure and venous return; increased capillary permeability shifts fluid out of the circulation.

Hormonal brakes. inhibit aldosterone secretion from the adrenal, vasopressin release, and sympathetic nerve activity — directly opposing the systems that drive fluid retention in heart failure.

Heart and metabolism. anti-fibrotic and anti-hypertrophic effects on heart muscle; in fat tissue, natriuretic peptides stimulate lipolysis and "browning" — one reason low natriuretic-peptide levels in obesity are of research interest.

Breakdown. neprilysin (neutral endopeptidase) and NPR-C clearance. Blocking neprilysin raises ANP, BNP and CNP levels — but also raises bradykinin (#169) and angiotensin II, which is why sacubitril is always paired with an angiotensin-receptor blocker.

ANP, BNP and CNP at a receptor that is itself a guanylate cyclase. Vessels relax, and the kidney lets sodium and water go — the body's own counterweight to fluid overload.Schematic — not to scale

3What the research shows

BNP and NT-proBNP as diagnostic and prognostic markers

The Breathing Not Properly study (Maisel 2002, NEJM; 1,586 emergency patients) showed BNP distinguished heart failure from other causes of breathlessness with ~90% sensitivity at 100 pg/mL. The PRIDE study did the same for NT-proBNP (Januzzi 2005, Am J Cardiol). Both are now embedded in every major heart-failure guideline for diagnosis, prognosis and, in some settings, to guide treatment intensity. Levels are lower in obesity and higher with age, kidney disease and atrial fibrillation, which complicates interpretation. [3][4]

Neprilysin inhibition (raising endogenous natriuretic peptides)

PARADIGM-HF (McMurray 2014, NEJM; 8,442 patients with heart failure and reduced ejection fraction) compared sacubitril/valsartan with enalapril and was stopped early for benefit: a 20% relative risk reduction in cardiovascular death or heart-failure hospitalisation. This is the strongest evidence that boosting the natriuretic-peptide system helps. In preserved ejection fraction (PARAGON-HF, Solomon 2019, NEJM) the benefit narrowly missed statistical significance. [5][6]

Graded A (neutral)

Recombinant BNP (nesiritide) in acute heart failure

Early studies showed nesiritide lowered filling pressures and eased breathlessness (VMAC 2002, JAMA), but meta-analyses in 2005 raised concerns about kidney injury and mortality. ASCEND-HF (O'Connor 2011, NEJM; n=7,141) settled it: no meaningful improvement in breathlessness, no effect on death or rehospitalisation, no kidney harm, but more hypotension. Nesiritide remains approved but is seldom used. See #137. [7]

Graded B/A (mixed)

Recombinant ANP (carperitide) in acute heart failure

Carperitide is widely used in Japan on the basis of haemodynamic improvement and observational registries. The randomised LOW-HF trial (Nagai 2021 / Matsue 2022, Circ Heart Fail †) found that low-dose carperitide did not improve outcomes versus standard care, and some Japanese registry analyses have associated it with worse short-term outcomes, likely confounded. It remains marketed in Japan only.

Graded B/C

ANP/BNP in kidney protection, sepsis and metabolism

Small trials of low-dose ANP to protect the kidney after cardiac surgery or contrast exposure showed reduced acute kidney injury in some studies (Nigwekar 2009 meta-analysis, Clin J Am Soc Nephrol) but are not practice-changing. Observational and mechanistic work links low natriuretic-peptide levels to obesity, insulin resistance and hypertension ("natriuretic handicap"), with rodent data showing ANP promotes fat burning. [9]

Designer natriuretic peptides

Chimeric peptides such as cenderitide (CD-NP, a CNP/DNP hybrid) and ANX-042 reached Phase 1–2 for heart failure and kidney disease; none has progressed to approval †.

4Reported side effects and interactions

Literature-reported

Literature (infused ANP/BNP). hypotension is the main effect — dose-dependent, sometimes prolonged with nesiritide; headache, nausea, dizziness, bradycardia; transient rises in creatinine, particularly when combined with aggressive diuresis or in low-pressure states. ASCEND-HF found no excess kidney injury or death with nesiritide at approved doses.

Literature (sacubitril/valsartan). hypotension, hyperkalaemia, cough, kidney function changes; angioedema (bradykinin-related) more common than with valsartan alone, and the combination is contraindicated within 36 hours of an ACE inhibitor.

Community-reported

none documented.

Theoretical. chronic elevation of natriuretic peptides via neprilysin inhibition raises questions about amyloid-β handling in the brain (neprilysin also degrades Aβ); the PERSPECTIVE trial (2022) found no cognitive harm over three years †.

Interactions. additive hypotension with diuretics, nitrates, ACE inhibitors and ARBs; ACE inhibitor plus neprilysin inhibitor gives unacceptable angioedema risk.

Markers researchers commonly monitor

Here the peptides are themselves the markers:

Marker	Why it's watched
BNP and NT-proBNP	diagnosis and prognosis of heart failure; falling levels during treatment predict better outcomes. Note: sacubitril raises BNP (it blocks its breakdown) but not NT-proBNP, so NT-proBNP is the marker to follow on that drug.
Blood pressure	hypotension is the dose-limiting effect of any natriuretic-peptide infusion.
Serum creatinine, eGFR, urea	kidney function during infusion and on neprilysin inhibitors.
Serum potassium and sodium	natriuresis and RAAS suppression both shift electrolytes.
Urine output and body weight	the direct read-out of natriuretic effect.
Mid-regional pro-ANP (MR-proANP)	a research and some-clinical alternative to NT-proBNP.
Echocardiographic filling pressures / pulmonary capillary wedge pressure	in haemodynamic studies.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Carperitide and nesiritide are supplied as hospital vials and diluted into infusion solutions by pharmacy or nursing staff according to the label, for use under continuous blood-pressure monitoring. Native ANP and BNP for research are lyophilised peptides stored frozen and dissolved immediately before use. No self-administered form exists; the site calculator is not applicable.

6Commonly studied alongside

Nesiritide (#137, the recombinant BNP product), carperitide, sacubitril/valsartan and other neprilysin inhibitors, vosoritide and CNP (same family, different receptor), bradykinin (#169 — also a neprilysin substrate, and the cause of the angioedema signal), angiotensin II and aldosterone (the opposing systems), loop diuretics and SGLT2 inhibitors (the heart-failure treatments natriuretic-peptide drugs are compared with and layered on). NT-proBNP is the outcome marker in most GLP-1 heart-failure trials (semaglutide, STEP-HFpEF).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Native ANP/BNP not marketed. Nesiritide (Natrecor) FDA-approved 2001 for acute decompensated heart failure, little used. Sacubitril/valsartan (Entresto) FDA-approved 2015, expanded 2021. Carperitide not approved
European Union	Nesiritide never authorised; carperitide not authorised; sacubitril/valsartan authorised 2015
United Kingdom	As EU; sacubitril/valsartan NICE-recommended for HFrEF
Australia	Sacubitril/valsartan TGA-registered and PBS-listed; nesiritide and carperitide not registered
South Africa	Sacubitril/valsartan registered with SAHPRA †; recombinant natriuretic peptides not registered
Japan	Carperitide (Hanp) approved 1995 for acute heart failure — the only country where recombinant ANP is marketed
Sport	Not listed by WADA; diuretic effect is physiological and short-lived †

8Open questions

Why did giving the hormone directly (nesiritide, carperitide) fail to improve outcomes when protecting the body's own hormone (neprilysin inhibition) succeeded?
Can natriuretic-peptide pathway drugs help in heart failure with preserved ejection fraction, where PARAGON-HF narrowly missed?
Does low natriuretic-peptide activity contribute to obesity-related hypertension, and can it be targeted?
Will designer natriuretic peptides with longer or receptor selectivity find a role?

9References

1de Bold AJ et al. (1981). A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci. DOI
2Sudoh T et al. (1988). A new natriuretic peptide in porcine brain. Nature. PubMed · DOI
3Maisel AS et al. (2002). Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. NEJM. PubMed · DOI
4Januzzi JL et al. (2005). The N-terminal pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol. PubMed · DOI
5McMurray JJV et al. (2014). Angiotensin–neprilysin inhibition versus enalapril in heart failure (PARADIGM-HF). NEJM. PubMed · DOI
6Solomon SD et al. (2019). Angiotensin–neprilysin inhibition in heart failure with preserved ejection fraction (PARAGON-HF). NEJM. PubMed · DOI
7O'Connor CM et al. (2011). Effect of nesiritide in patients with acute decompensated heart failure (ASCEND-HF). NEJM. PubMed · DOI
8Publication Committee for the VMAC Investigators (2002). Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA. PubMed
9Nigwekar SU et al. (2009). Atrial natriuretic peptide for management of acute kidney injury: a systematic review and meta-analysis. Clin J Am Soc Nephrol. PubMed · DOI
10Goetze JP et al. (2020). Cardiac natriuretic peptides. Nat Rev Cardiol. PubMed · DOI
11Potter LR, Abbey-Hosch S, Dickey DM (2006). Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. Endocr Rev. PubMed · DOI

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

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