NEP inhibitor SQ 28603 enhanced both ANP effects in monkeys and BNP effects in hypertensive rats, validating the strategy behind modern heart failure drugs.
ANP + BNP potentiatedNEP inhibition enhanced both natriuretic peptides, the strategy behind the heart failure drug Entresto
What the researchers found
SQ 28603 potentiated both ANP effects in monkeys (increased plasma ANP, sodium excretion) and BNP effects in hypertensive rats (blood pressure lowering, renal responses).
Why it matters
NEP inhibitors protect the body's own blood pressure-lowering peptides from breakdown. This strategy became the basis for sacubitril/valsartan (Entresto), now a leading heart failure treatment.
How the study worked
Conscious monkeys received ANP infusion with or without SQ 28603. Conscious spontaneously hypertensive rats received BNP with or without NEP inhibitor. Measured plasma ANP, cGMP, sodium excretion, and blood pressure.
What this study cannot tell us
Animal studies in monkeys and rats. Exogenous peptide infusion does not perfectly replicate endogenous natriuretic peptide physiology.
How to read the evidence
Moderate — controlled animal studies in two species (monkeys and rats) with relevant disease model (spontaneous hypertension).
When this study was published
Published in 1995. This research helped establish the rationale for neprilysin inhibitors. Sacubitril (an NEP inhibitor) combined with valsartan became Entresto, FDA-approved in 2015 for heart failure.
The bigger picture
This research validated a concept that became one of the most important cardiovascular drug strategies in decades. By protecting natriuretic peptides from breakdown, NEP inhibitors led to sacubitril/valsartan (Entresto), which significantly reduces heart failure deaths.
Questions still open
- Can NEP inhibition alone provide sufficient blood pressure and heart failure benefit, or is combination therapy always needed?
- What other beneficial peptides are protected by NEP inhibition beyond ANP and BNP?
Common questions
What are natriuretic peptides?
How does this relate to Entresto?
Read the original research
Potentiation of natriuretic peptides by neutral endopeptidase inhibitors.
Clinical and experimental pharmacology & physiology, 22(1), 63-9
Citation
Seymour, A A; Abboa-Offei, B E; Smith, P L; Mathers, P D; Asaad, M M; Rogers, W L. (1995). Potentiation of natriuretic peptides by neutral endopeptidase inhibitors.. Clinical and experimental pharmacology & physiology, 22(1), 63-9.