Sacubitril/valsartan (LCZ696) improves outcomes in HFrEF. Sacubitril inhibits neprilysin. Which peptides accumulate as a direct result of neprilysin inhibition?
- A Angiotensin II and endothelin-1
- B Aldosterone and renin
- C BNP, ANP, bradykinin, and substance P ✓
- D Vasopressin and oxytocin
Correct answer: C. BNP, ANP, bradykinin, and substance P
Explanation
Neprilysin (neutral endopeptidase) degrades natriuretic peptides (BNP, ANP), bradykinin, substance P, and adrenomedullin. Sacubitril inhibition of neprilysin raises levels of these vasodilatory, natriuretic, and anti-fibrotic peptides. However, neprilysin also degrades angiotensin II, so inhibiting it alone would elevate angiotensin II — hence valsartan (ARB) is combined to block this effect. Increased bradykinin contributes to the slight risk of angioedema seen with sacubitril/valsartan.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.