Natriuretic peptides are a family of hormones produced naturally within the human body. These peptides play a role in maintaining fluid balance, blood pressure, and heart function. They act as messengers that help different organ systems communicate to keep the body’s internal environment stable. Their actions are broad, influencing the kidneys, blood vessels, and endocrine glands.
Types of Natriuretic Peptides
There are three main types of natriuretic peptides: atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Each type originates from different parts of the body and has distinct primary functions.
Atrial natriuretic peptide (ANP) is primarily synthesized and stored in the specialized cells of the heart’s upper chambers, known as the atria. When blood pressure or blood volume increases, these atrial cells stretch, leading to the release of ANP into the bloodstream. ANP’s main action is to promote the excretion of sodium and water by the kidneys, which helps to reduce blood volume and lower blood pressure. It also contributes to relaxing blood vessels.
B-type natriuretic peptide (BNP), despite its name, is predominantly produced by the ventricles, the lower chambers of the heart. Its release is triggered by increased stretch and stress on the ventricular walls, often due to conditions like heart failure. BNP’s functions mirror those of ANP, including promoting sodium and water excretion and vasodilation, but it is particularly sensitive to ventricular strain. This makes it a useful indicator of heart health.
C-type natriuretic peptide (CNP) differs from ANP and BNP in its primary sites of production and main functions. CNP is found in various tissues, including the brain, blood vessel lining (endothelium), and bones. Unlike ANP and BNP, CNP has less direct impact on sodium and water balance. Its primary role involves regulating blood vessel tone and promoting bone growth.
How Natriuretic Peptides Signal
Natriuretic peptides exert their effects by binding to specific receptor proteins located on the surface of target cells. These receptors act like locks, and the natriuretic peptides are the keys that fit into them. This binding initiates a series of events inside the cell, transmitting the signal from outside to inside.
The two primary receptors for natriuretic peptides are Natriuretic Peptide Receptor-A (NPRA) and Natriuretic Peptide Receptor-B (NPRB). ANP and BNP primarily bind to NPRA, while CNP predominantly binds to NPRB. Upon activation, these receptors undergo a change that stimulates an enzyme called guanylyl cyclase, which is part of the receptor itself.
Activation of guanylyl cyclase leads to the conversion of guanosine triphosphate (GTP) into cyclic guanosine monophosphate (cGMP) inside the cell. Cyclic GMP then acts as a “second messenger” within the cell. For instance, increased cGMP levels can relax smooth muscle cells in blood vessels, leading to vasodilation, or alter kidney cell function to promote fluid excretion.
Natriuretic Peptides and Body Regulation
Natriuretic peptides play a central role in regulating several bodily systems. Their actions primarily focus on managing fluid volume, blood pressure, and the overall health of the cardiovascular system.
In the kidneys, natriuretic peptides promote the excretion of sodium and water, a process known as natriuresis and diuresis, respectively. ANP and BNP increase the glomerular filtration rate, which is the speed at which blood is filtered by the kidneys. This enhanced filtration, combined with reduced reabsorption of sodium in the kidney tubules, leads to a greater output of urine, effectively reducing overall blood volume.
Beyond their effects on the kidneys, natriuretic peptides also influence the vascular system. They cause vasodilation, meaning they relax and widen blood vessels. This relaxation reduces resistance to blood flow, thereby lowering blood pressure.
Natriuretic peptides also interact with the body’s endocrine system, specifically by inhibiting the renin-angiotensin-aldosterone system (RAAS). The RAAS is a powerful system that normally works to raise blood pressure and retain fluid. By counteracting its effects, natriuretic peptides reduce the release of hormones like renin and aldosterone, which would otherwise promote sodium retention and blood vessel constriction. This inhibitory action further supports their role in lowering blood pressure and reducing fluid overload.
Natriuretic Peptides in Health and Disease
Natriuretic peptides are present in the body in healthy states, contributing to the normal regulation of fluid and blood pressure. Their levels typically remain within a certain range, reflecting the balanced functioning of the cardiovascular system. However, their concentrations can change significantly in various disease conditions.
In conditions like heart failure, the heart struggles to pump blood effectively, leading to increased pressure and stretch within its chambers. This elevated stress causes a substantial increase in the production and release of BNP from the heart’s ventricles. Measuring BNP levels in the blood is therefore a widely used method for diagnosing and monitoring the severity of heart failure. Higher BNP levels correlate with more severe heart failure and poorer outcomes.
Natriuretic peptides also play a role in hypertension, or high blood pressure. While ANP and BNP work to lower blood pressure, their effectiveness can be overwhelmed in chronic hypertension. Some forms of hypertension may involve a reduced sensitivity to natriuretic peptides or increased breakdown of these hormones. This imbalance contributes to the sustained elevation of blood pressure in affected individuals.
Cardiac hypertrophy, a condition where the heart muscle thickens, also involves changes in natriuretic peptide levels. The heart increases ANP and BNP production to counteract the increased workload. These peptides also have direct anti-growth effects on heart muscle cells, helping to prevent excessive thickening.
Medical Applications of Natriuretic Peptides
The understanding of natriuretic peptide function has led to progress in medical diagnostics and therapeutic strategies. Their presence and varying levels in the bloodstream provide valuable information about a patient’s cardiovascular health.
One of the most widespread medical applications is the use of BNP and its inactive precursor, N-terminal pro-B-type natriuretic peptide (NT-proBNP), as diagnostic biomarkers. A blood test measuring these peptides helps doctors diagnose heart failure, differentiate it from other causes of shortness of breath, and assess its severity. These tests are also used to monitor a patient’s response to heart failure treatment and predict future risks.
Beyond diagnosis, the natriuretic peptide system has become a target for therapeutic interventions. Sacubitril/valsartan, a widely used medication for heart failure, works by inhibiting an enzyme called neprilysin. Neprilysin is responsible for breaking down natriuretic peptides, so by blocking it, the medication increases the circulating levels of ANP and BNP. This leads to sustained vasodilation, reduced fluid retention, and a decrease in cardiac stress.
Other therapeutic strategies aim to mimic the effects of natriuretic peptides directly. While synthetic forms of ANP and BNP have been explored, their clinical application has faced challenges.