Atrial Natriuretic Peptide (ANP), often called Atrial Natriuretic Factor (ANF), is a hormone produced by the heart that maintains fluid balance and regulates blood pressure. Its discovery in the 1980s showed that the heart, traditionally viewed only as a pump, also functions as an endocrine organ. ANP belongs to the family of natriuretic peptides, defined by their ability to induce the excretion of sodium from the body. The fundamental function of ANP is to act as a counter-regulatory force against systems that raise blood pressure, serving as a rapid-response mechanism to prevent excessive volume overload.
Synthesis and Triggers for ANP Release
The primary source of Atrial Natriuretic Peptide is the cardiac muscle cells, or cardiomyocytes, found within the walls of the heart’s upper chambers, the atria. ANP is stored in specialized secretory granules within these atrial cells as a precursor protein called proANP. This storage allows the heart to quickly release a large amount of active hormone when stimulated.
The most potent and direct trigger for ANP release is the mechanical stretching of the atrial wall. This stretching occurs when the volume of blood returning to the heart is high, a condition known as hypervolemia, or when systemic blood pressure is elevated. The atrial muscle fibers contain mechanoreceptors that sense this increase in wall tension, signaling the release of the stored proANP into the bloodstream.
Once released, proANP is rapidly cleaved into the biologically active 28-amino-acid peptide by the enzyme corin, a transmembrane serine protease. This cleavage converts the inactive storage form into the potent hormone that travels through the circulation to target organs. This rapid process ensures the body can quickly respond to sudden changes in blood volume or pressure.
How ANP Regulates Fluid and Blood Pressure
ANP exerts its influence through a multi-pronged mechanism targeting the kidneys, blood vessels, and other hormone systems to reduce blood volume and vascular resistance. The hormone binds to Natriuretic Peptide Receptor-A (NPR-A) on target cells, activating the intracellular messenger cyclic guanosine monophosphate (cGMP). This second messenger mediates all the downstream effects that lead to lower blood pressure.
Kidney Action
The most significant action of ANP occurs in the kidneys, promoting the loss of sodium (natriuresis) and water (diuresis). ANP enhances the kidney’s filtration capacity by acting on the small blood vessels within the glomerulus. It causes the afferent arteriole (supplying blood) to dilate, while simultaneously causing the efferent arteriole (draining blood) to constrict.
This dual action significantly increases pressure within the glomerular capillaries, boosting the Glomerular Filtration Rate (GFR) and pushing more fluid into the forming urine. Furthermore, ANP directly inhibits the reabsorption of sodium in several segments of the nephron. By preventing the kidneys from reclaiming sodium, it ensures that water follows the sodium out of the body, effectively reducing the overall circulating fluid volume.
Vascular Action
ANP also directly affects the tone of blood vessels, contributing to a reduction in systemic blood pressure. The hormone causes the smooth muscle cells in the walls of arteries and veins to relax, resulting in vasodilation. This widening of blood vessels decreases the total peripheral resistance against which the heart must pump blood.
The resulting decrease in resistance and blood pressure complements the volume-reducing effects of the kidneys. This vascular relaxation is mediated by the increase in cGMP within the smooth muscle cells.
Hormonal Inhibition
A third function of ANP is counteracting major hormone systems that increase blood pressure and fluid retention. The hormone suppresses the Renin-Angiotensin-Aldosterone System (RAAS), a powerful regulator of fluid balance and vasoconstriction. ANP specifically inhibits the release of renin from the kidney, the first step in the RAAS cascade.
By inhibiting renin, ANP prevents the formation of Angiotensin II and the subsequent release of aldosterone from the adrenal glands. Since aldosterone promotes sodium and water reabsorption, its inhibition by ANP further enhances excretion. ANP also dampens the release and action of Vasopressin (Antidiuretic Hormone or ADH), which normally conserves water.
ANP Peptides as Clinical Biomarkers
While ANP is the original natriuretic peptide, its short half-life (two to five minutes) limits its usefulness as a practical clinical test. Therefore, the related B-type Natriuretic Peptide (BNP) and its inactive fragment, N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), are the standard biomarkers in clinical practice. BNP is predominantly released by the heart’s ventricles in response to increased tension and stretch, similar to ANP release from the atria.
Measuring circulating levels of BNP or NT-proBNP is a cornerstone of modern diagnosis and management of heart failure. Elevated levels indicate the heart muscle is under stress and experiencing significant wall tension due to volume or pressure overload. A blood test for these biomarkers is routinely used to distinguish between shortness of breath caused by heart failure and that caused by non-cardiac issues, such as lung disease.
The concentration of these peptides correlates directly with the severity of heart failure, making them valuable for assessing disease progression and prognosis. Monitoring NT-proBNP levels can guide medical therapy, as a decrease suggests treatment is effectively reducing strain on the heart. Synthetic versions, such as recombinant human ANP (carperitide), have also been developed for therapeutic use to manage acute decompensated heart failure by providing immediate volume and pressure reduction.