What they are
Natriuretic peptides are the body's counterweight to fluid overload. The name says what they do: natri- (sodium) -uretic (into the urine). When the heart is stretched by too much blood volume, these hormones make the kidneys excrete sodium and water and make blood vessels relax, lowering the load.
There are four in humans, all short peptides cut from longer precursor proteins, and all built around the same feature: a 17-residue ring closed by a single disulfide bond — UniProt places it at precursor positions 130–146 in ANP, 112–128 in BNP and 110–126 in CNP.
The family, one by one
| Peptide | Length | Where it is made | Precursor (UniProt) | Library entry |
|---|---|---|---|---|
| ANP (atrial natriuretic peptide) | 28 | Heart atria | NPPA, residues 124–151 (P01160) | ANP |
| Urodilatin | 32 | Kidney (distal tubules) | NPPA, residues 120–151 (P01160) | — |
| BNP (B-type natriuretic peptide) | 32 | Heart ventricles, under stretch | NPPB, residues 103–134 (P16860) | BNP and NT-proBNP |
| CNP (C-type natriuretic peptide) | 22 or 53 | Several tissues; acts locally, including bone growth plates | NPPC, 105–126 or 74–126 (P23582) | via vosoritide |
Two points the table makes visible. Urodilatin is ANP with four extra residues at the front — both come from the same precursor, cut at different places. And BNP's precursor splits into two pieces: BNP itself and a 76-residue inactive fragment, NT-proBNP, which matters because the two behave differently in the blood (see below).
The first sign the family existed came from the heart itself: in 1981, de Bold reported that extract of rat atria made the kidneys excrete sodium.
How they act
All four act on natriuretic peptide receptors on cell surfaces; ANP and BNP mainly drive salt and water loss and vessel relaxation, while CNP acts closer to where it is made, including on growth-plate cartilage cells in bone (UniProt P23582) — the reason a CNP analogue treats a growth disorder. UniProt records that urodilatin, not ANP, may be the natriuretic peptide that regulates sodium and water handling inside the kidney. They are cleared partly by the enzyme neprilysin, which is the hinge of the one modern drug class in the family.
Two infused copies that failed
The obvious idea — give people more of the hormone during acute heart failure — was tested twice at scale:
| Drug | What it is | Trial | Patients | Main result |
|---|---|---|---|---|
| Nesiritide (Natrecor) | A copy of BNP | ASCEND-HF (O'Connor 2011, NEJM, PMID 21732835) | 7,141 | Death or HF rehospitalisation at 30 days 9.4% vs 10.1% (P = 0.31); dyspnoea gains below the pre-set threshold; more hypotension |
| Ularitide | Synthetic urodilatin | TRUE-AHF (Packer 2017, NEJM, PMID 28402745) | 2,157 | Cardiovascular death 21.7% vs 21.0% over a median 15 months (HR 1.03) |
Both drugs lowered blood pressure, and ularitide lowered NT-proBNP — "favorable physiological effects," as the TRUE-AHF authors put it — without changing what happened to patients. Nesiritide had been approved in 2001 on symptom data; after ASCEND-HF the authors wrote that it "cannot be recommended for routine use." It is now listed discontinued. Ularitide was never approved.
What reached patients instead
- A blood test. BNP and NT-proBNP are measured to help diagnose and follow heart failure. The library's BNP and NT-proBNP entry explains why the two numbers differ and why only the treating clinician can read them.
- A breakdown blocker. Rather than infusing the hormone, sacubitril slows its destruction. The Entresto label: sacubitril's active metabolite inhibits neprilysin, and the drug's effects "are attributed to the increased levels of peptides that are degraded by neprilysin, such as natriuretic peptides," together with valsartan. Entresto was approved on 2015-07-07; generic sacubitril/valsartan has been listed since 2024.
- A growth drug. Vosoritide (Voxzogo, 2021) is a 39-residue CNP analogue approved for achondroplasia.
Where they stand
- The hormones themselves: made by everyone; not sold.
- Nesiritide: approved 2001-08-10 (NDA 020920); Discontinued, with an FDA determination that this was not for safety or effectiveness reasons (Drugs@FDA, 2026-11-03).
- Ularitide: no approval; TRUE-AHF neutral.
- Sacubitril/valsartan: prescription (15 applications listed in all, Entresto NDA 207620 among them, 2026-11-03).
- Research record: 37,623 PubMed records (2026-11-03).
Related reading
Each member with its own entry: ANP, BNP and NT-proBNP and the CNP analogue vosoritide. The hormone that pushes the other way, holding water in, is vasopressin. How a ring closed by a disulfide bond changes a peptide is explained in the peptide bond entry.