History of Atrial Natriuretic Peptide
| Category | Research |
|---|---|
| Also known as | ANP history, atrial natriuretic factor, de Bold ANP |
| Last updated | 2026-04-14 |
| Reading time | 3 min read |
| Tags | historyanpbnpnatriuretic-peptidesheart-failure |
Overview
Atrial natriuretic peptide (ANP) is a 28-amino-acid peptide hormone secreted primarily from atrial cardiomyocytes in response to volume expansion and atrial stretch. Its identification in 1981 by Adolfo de Bold at Queen's University in Kingston, Ontario, was a landmark moment in cardiovascular physiology. De Bold injected extracts of rat atrial tissue into other rats and observed rapid, massive diuresis and natriuresis — establishing for the first time that the heart is an endocrine organ, not merely a mechanical pump.
The active peptide was isolated and sequenced over the next several years. Related family members were soon identified: brain natriuretic peptide (BNP, despite its name, comes mainly from the ventricles) and C-type natriuretic peptide (CNP, from the endothelium). All three act through guanylyl cyclase-coupled natriuretic peptide receptors (NPR-A, NPR-B, NPR-C) to produce vasodilation, natriuresis, and antagonism of the renin-angiotensin-aldosterone system.
Measurement of BNP (and its co-secreted fragment NT-proBNP) has become a cornerstone of heart failure diagnosis, prognosis, and management. The natriuretic peptide system has also become a direct therapeutic target.
Key People
- Adolfo J. de Bold: Canadian-Argentine physiologist who identified ANP.
- Philip Needleman: Contributed to ANP structural and pharmacological studies.
- Tadashi Inagami and Tanenao Eto: Japanese researchers involved in natriuretic peptide characterization.
- John C. Burnett Jr.: Led extensive clinical work on natriuretic peptides and heart failure at Mayo Clinic.
Timeline
- 1956: Kisch observes electron-dense granules in atrial cardiomyocytes.
- 1981: De Bold publishes the natriuretic effect of atrial extracts.
- 1984: Full structures of ANP from multiple species are determined.
- 1988: BNP is identified in porcine brain; later recognized as a cardiac hormone.
- 1990: CNP is discovered.
- 2001: Nesiritide (recombinant BNP) approved for acute decompensated heart failure.
- 2015: Sacubitril/valsartan, which inhibits neprilysin (a natriuretic peptide-degrading enzyme) and angiotensin II, is approved for heart failure.
Background
Before 1981, the idea that the heart could be a source of hormones was largely unexplored, though Kisch's 1956 electron microscopy had hinted that atrial cardiomyocytes contained secretory granules unusual for muscle cells. De Bold's contribution was to ask a simple physiological question: what happens if you inject atrial tissue extracts into an animal? The dramatic natriuretic response changed cardiovascular physiology.
The natriuretic peptide system is now understood to oppose the renin-angiotensin-aldosterone and sympathetic nervous systems. It promotes salt and water excretion, vasodilation, reduced sympathetic tone, and inhibition of remodeling. In heart failure, circulating levels of ANP, BNP, and NT-proBNP rise substantially, reflecting cardiac stress, and they are used clinically as diagnostic and prognostic biomarkers.
Modern Relevance
Natriuretic peptides are central to heart failure care. BNP and NT-proBNP assays guide diagnosis, risk stratification, and titration of therapy. Sacubitril/valsartan augments endogenous natriuretic peptide activity by blocking neprilysin, the enzyme that degrades them, while simultaneously inhibiting the renin-angiotensin system through valsartan. This combination has become a mainstay of heart failure with reduced ejection fraction.
Beyond heart failure, the natriuretic peptide system is studied in hypertension, obesity, and metabolic disease, where CNP and modified ANP-based drugs (e.g., vosoritide for achondroplasia) have expanded the therapeutic footprint. The success of natriuretic peptide biology is a direct descendant of de Bold's 1981 experiment.
Related Compounds
Related entries
- History of Angiotensin Research— The angiotensin peptides emerged from parallel Argentine and American research in the 1930s-1950s that revealed the renin-angiotensin-aldosterone system.
- The Discovery of Endothelin— Endothelin-1, one of the most potent vasoconstrictors known, was identified in 1988 by Masashi Yanagisawa in Tsukuba.
- The Discovery of Vasopressin— Vasopressin, the antidiuretic hormone of the posterior pituitary, was identified through late 19th- and early 20th-century research on pituitary extracts.