Natriuretic peptides (NPs) are a family of hormones the body uses to maintain a healthy balance of fluid and blood pressure. These molecules are produced primarily by the heart and the brain, acting as a natural defense system against high blood pressure and excessive fluid retention. These peptides are constantly released into the bloodstream, where they signal to various organs, particularly the kidneys and blood vessels, to adjust fluid levels and vascular tone.
The Major Types and Their Origins
The natriuretic peptide family is comprised of three main types, each with distinct origins and roles within the body. Atrial Natriuretic Peptide (ANP) is synthesized and stored predominantly in the muscle cells of the heart’s upper chambers, the atria. ANP is released rapidly in response to atrial stretch, which occurs when the heart experiences an increase in blood volume or pressure.
B-type Natriuretic Peptide (BNP) is primarily produced by the muscle cells of the heart’s main pumping chambers, the ventricles. While initially discovered in porcine brain tissue, the ventricular release of BNP is most significant in human physiology. BNP synthesis and secretion increase when the ventricular wall is stretched or stressed due to conditions like volume overload or pump dysfunction.
C-type Natriuretic Peptide (CNP) differs from the other two because it is not primarily a cardiac hormone. CNP is produced mainly by the cells lining blood vessels, known as the vascular endothelium, and also within the central nervous system. Its function is often more localized, acting primarily in a paracrine manner to influence the tone of blood vessels.
Physiological Role in Fluid and Blood Pressure Regulation
Natriuretic peptides operate as counter-regulatory hormones to maintain balance. Their core action is to promote natriuresis (sodium excretion) and diuresis (water excretion).
In the kidneys, ANP and BNP increase the glomerular filtration rate by dilating the afferent arteriole and constricting the efferent arteriole, thereby increasing the amount of fluid filtered. The peptides also directly inhibit the reabsorption of sodium and water within the renal tubules, resulting in a greater loss of salt and fluid from the body. This process ultimately reduces the total blood volume, which decreases the strain on the heart.
NPs are vasodilators. This vasodilation leads to a widening of the blood vessels, which lowers systemic vascular resistance and reduces blood pressure. Natriuretic peptides also act to antagonize the Renin-Angiotensin-Aldosterone System (RAAS), a hormonal cascade that typically works to raise blood pressure and retain fluid. By inhibiting the release of renin and aldosterone, NPs effectively block the RAAS’s attempt to constrict blood vessels and conserve sodium.
Diagnostic Significance in Heart Health
The concentration of natriuretic peptides in the blood serves as a clinical tool, particularly in heart failure. BNP and its inactive precursor fragment, N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), are measured to help diagnose and monitor the severity of heart failure. An elevated level of these peptides indicates increased stress and wall tension in the ventricles, characteristic of a failing heart that cannot effectively pump blood forward.
In patients presenting with shortness of breath, a low NT-proBNP level, typically less than 300 picograms per milliliter (pg/mL) in an acute setting, makes a diagnosis of heart failure highly unlikely. Conversely, levels above this threshold strongly suggest heart failure as the cause of the symptoms. Higher concentrations correlate with more severe cardiac pump dysfunction and a less favorable prognosis.
The specific diagnostic cut-offs are adjusted based on patient age, as NP levels naturally increase over a person’s lifespan. In an outpatient setting, a value of less than 125 pg/mL for NT-proBNP is used to exclude heart failure. Clinicians use these measurements to differentiate cardiac causes of breathlessness from non-cardiac causes, such as lung disease, guiding subsequent treatment decisions.
Therapeutic Development
The recognition of natriuretic peptides as the body’s protective mechanism against volume overload has led to the development of pharmacological treatments for heart failure. One approach involves using synthetic versions of the natural peptides, such as nesiritide, which is a recombinant form of human BNP. This drug was designed to be administered intravenously to patients with acute decompensated heart failure to rapidly induce vasodilation and diuresis.
A more successful and widely adopted strategy involves a class of drugs called neprilysin inhibitors. Neprilysin is an enzyme that circulates and breaks down natriuretic peptides, ending their beneficial effects. Inhibiting this enzyme prolongs the activity of the body’s own ANP and BNP, augmenting their protective effects.
Sacubitril is a neprilysin inhibitor that is combined with the angiotensin receptor blocker valsartan to form a single medication. This combination therapy, known as an Angiotensin Receptor-Neprilysin Inhibitor (ARNI), is a standard treatment for chronic heart failure with reduced ejection fraction. The dual action enhances the positive effects of NPs while simultaneously blocking the harmful effects of the overactive RAAS, leading to improved outcomes for patients.