Neprilysin inhibitors are a class of medications used to manage cardiovascular conditions. These drugs influence the body’s natural systems by interacting with specific enzymes. This action supports heart health and helps maintain proper fluid balance, improving overall cardiac well-being.
Understanding Neprilysin
Neprilysin is a naturally occurring enzyme found throughout the human body, particularly in the kidneys, lungs, and heart. Its primary role involves breaking down a variety of peptides, which are small chains of amino acids that act as signaling molecules. This enzyme’s activity helps regulate many bodily functions, including blood pressure and fluid balance.
Among the peptides neprilysin degrades are natriuretic peptides, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). These specific peptides are released by the heart in response to increased pressure or volume. They naturally promote the excretion of sodium and water from the body, helping to lower blood pressure and reduce fluid overload.
Neprilysin also breaks down other important substances, including bradykinin and angiotensin II. Bradykinin is a peptide that contributes to vasodilation, the widening of blood vessels, which can help lower blood pressure. Conversely, angiotensin II is a potent vasoconstrictor, meaning it narrows blood vessels, thereby increasing blood pressure. The enzyme’s broad activity highlights its widespread influence on cardiovascular regulation.
How Neprilysin Inhibitors Work
Neprilysin inhibitors function by blocking the activity of the neprilysin enzyme, thereby preventing it from breaking down certain beneficial peptides. This inhibition leads to an increase in the levels of these peptides within the bloodstream. Elevated concentrations of natriuretic peptides, for instance, enhance their natural effects on the body.
Increased natriuretic peptide levels promote vasodilation, causing blood vessels to relax and widen, which helps to lower blood pressure. They also stimulate natriuresis, which is the increased excretion of sodium through urine, and diuresis, the increased production and excretion of urine. These combined actions reduce the volume of fluid in the body and decrease the workload on the heart.
A key aspect of neprilysin inhibitor therapy involves combining them with angiotensin receptor blockers (ARBs), such as in the medication sacubitril-valsartan. This combination addresses a potential consequence of neprilysin inhibition. While neprilysin breaks down beneficial natriuretic peptides, it also degrades angiotensin II, a peptide that can cause blood vessel constriction and fluid retention.
Inhibiting neprilysin alone would increase beneficial peptides but also lead to a rise in angiotensin II levels. To counteract this, an ARB blocks angiotensin II receptors. This dual action ensures the beneficial effects of increased natriuretic peptides are realized without the counteracting effects of elevated angiotensin II.
Clinical Applications and Benefits
Neprilysin inhibitors, particularly in combination with angiotensin receptor blockers, are primarily used in the management of specific cardiovascular conditions. A prominent application is in treating chronic heart failure with reduced ejection fraction (HFrEF). In this condition, the heart’s pumping ability is diminished, leading to symptoms like shortness of breath and fluid retention.
For individuals with HFrEF, these medications improve symptoms like fatigue and breathlessness, enhancing quality of life. The therapy also reduces heart failure-related hospitalizations.
Beyond heart failure, neprilysin inhibitors also help manage high blood pressure. By promoting vasodilation and natriuresis, they lower systemic blood pressure. This alleviates strain on the heart and blood vessels, reducing the risk of cardiovascular events.
Key Considerations for Treatment
Neprilysin inhibitor medications are prescribed by healthcare professionals after a thorough evaluation of a patient’s cardiovascular health. Ongoing medical monitoring assesses effectiveness and detects potential effects, ensuring appropriate therapy.
While beneficial, these medications may not suit everyone. A risk is angioedema, a rare but serious swelling of the face, lips, tongue, or throat. Individuals with a history of angioedema require careful assessment.
Effectiveness and suitability vary based on a patient’s health profile, including kidney and liver function. Dosage adjustments or alternative treatments may be necessary. Research continues to refine guidelines for optimal use.