Blocking the Enzyme That Destroys Heart-Protective Peptides Makes Them Work Much Better
An NEP inhibitor dramatically boosted the blood pressure-lowering and kidney effects of brain natriuretic peptide in both rats and monkeys.
Quick Facts
What This Study Found
NEP inhibitor SQ 28,603 markedly potentiated BNP-32 responses in SHR and monkeys. BNP was more resistant to NEP degradation than ANP. Cyclic GMP responses also potentiated.
Key Numbers
How They Did This
Conscious spontaneously hypertensive rats and cynomolgus monkeys received BNP or ANP with or without NEP inhibitor SQ 28,603. Blood pressure, natriuresis, and cyclic GMP were measured.
Why This Research Matters
This research laid groundwork for drugs like sacubitril (Entresto) that protect natriuretic peptides from degradation. These drugs are now standard heart failure treatment.
The Bigger Picture
This research directly led to the development of sacubitril/valsartan (Entresto), now a standard treatment for heart failure. By protecting the body's own heart-protective peptides from destruction, these drugs represent a paradigm shift in cardiovascular medicine.
What This Study Doesn't Tell Us
Animal study in two species. Doses and routes differ from clinical use. SHR model is one type of hypertension.
Questions This Raises
- ?Could NEP inhibitors benefit hypertension patients without heart failure?
- ?Are there other beneficial peptides that NEP inhibition could protect?
Trust & Context
- Key Stat:
- Markedly potentiated NEP inhibition dramatically enhanced BNP's blood pressure-lowering and natriuretic effects in two species
- Evidence Grade:
- Moderate — animal study in two species (rats and monkeys) with consistent results. Cross-species validation strengthens confidence.
- Study Age:
- Published in 1992 (34 years ago). This early work contributed to sacubitril/valsartan (approved 2015), now a cornerstone of heart failure treatment.
- Original Title:
- Potentiation of brain natriuretic peptides by SQ 28,603, an inhibitor of neutral endopeptidase 3.4.24.11, in monkeys and rats.
- Published In:
- The Journal of pharmacology and experimental therapeutics, 262(1), 60-70 (1992)
- Authors:
- Seymour, A A(2), Asaad, M M(2), Abboa-Offei, B E(2), Rovnyak, P L, Fennell, S, Rogers, W L
- Database ID:
- RPEP-00247
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What is NEP and why does blocking it help?
NEP (neutral endopeptidase) is an enzyme that breaks down natriuretic peptides — the body's natural heart-protective molecules. Blocking NEP lets these peptides last longer and work more effectively, lowering blood pressure and reducing fluid overload.
How did this lead to modern heart failure drugs?
This research showed that protecting BNP from enzymatic destruction dramatically boosted its cardiovascular benefits. This principle became sacubitril, which is combined with valsartan in the drug Entresto — now a standard treatment for heart failure.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-00247APA
Seymour, A A; Asaad, M M; Abboa-Offei, B E; Rovnyak, P L; Fennell, S; Rogers, W L. (1992). Potentiation of brain natriuretic peptides by SQ 28,603, an inhibitor of neutral endopeptidase 3.4.24.11, in monkeys and rats.. The Journal of pharmacology and experimental therapeutics, 262(1), 60-70.
MLA
Seymour, A A, et al. "Potentiation of brain natriuretic peptides by SQ 28,603, an inhibitor of neutral endopeptidase 3.4.24.11, in monkeys and rats.." The Journal of pharmacology and experimental therapeutics, 1992.
RethinkPeptides
RethinkPeptides Research Database. "Potentiation of brain natriuretic peptides by SQ 28,603, an ..." RPEP-00247. Retrieved from https://rethinkpeptides.com/research/seymour-1992-potentiation-of-brain-natriuretic
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.