What is the clinical evidence from this study?

Study design: Other. Population: Metabolism of atrial natriuretic peptide. Intervention: Phosphoramidon and aprotinin vs. Uninhibited state. Primary outcome: Half-life of ANP and ANP'.

What question did this study set out to answer?

To determine the distinct in vivo metabolic roles of endopeptidase 24.11 and kallikrein in the degradation of atrial natriuretic peptide (ANP) and its cleaved derivative in rats.

August 1, 1990Biochemical JournalOpen Access

Respective roles of kallikrein and endopeptidase 24.11 in the metabolic pathway of atrial natriuretic peptide in the rat

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Key result

In rats, the simultaneous administration of phosphoramidon and aprotinin maximally inhibited ANP degradation, increasing its half-life from 0.42 to 15 minutes.

Authors

YVYves VannesteUniversity of Liège SPStanislas PauwelsIntegral Consulting (United States)LLLuc LambotteUCLouvain

Discussion

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Implication

Caution against clinical use; leaves open dual protease inhibition to extend ANP action in cardiovascular research.

Key Points

To determine the distinct in vivo metabolic roles of endopeptidase 24.11 and kallikrein in the degradation of atrial natriuretic peptide (ANP) and its cleaved derivative in rats.
Infused 125I-labeled ANP and Cys-105-Phe-106-cleaved ANP (ANP') constantly into rats to assess plasma clearance kinetics.
Identified circulating peptide fragments using high-performance liquid chromatography (HPLC) fractionation.
Administered the endopeptidase inhibitor phosphoramidon and the kallikrein inhibitor aprotinin, individually and simultaneously, to quantify their effects on peptide degradation.
Circulating ANP and ANP' cleared rapidly under basal conditions, with mean half-lives of 0.42 min and 1.04 min, respectively, generating HPLC fragments characteristic of endopeptidase 24.11 cleavage.
Phosphoramidon extended ANP half-life to 7.8 min with intact peptide comprising >90% of circulating radioactivity, aprotinin extended it to 5.4 min, and co-administration increased half-life to 15 min.
Phosphoramidon had no measurable effect on the degradation of infused ANP', whereas aprotinin reduced the degradation rate of infused ANP' by more than 80%.

PICO

Population

Rats infused with 125I-labelled ANP and ANP' to study peptide metabolism and the effects of peptidase inhibitors.

Intervention / Comparator

Phosphoramidon and aprotinin vs Uninhibited state

Primary Outcome

Half-life of ANP and ANP'

Cite This Study

Vanneste et al. (1990) studied Metabolism of atrial natriuretic peptide. Phosphoramidon and aprotinin vs. Uninhibited state was evaluated on Half-life of ANP and ANP'. In rats, the simultaneous administration of phosphoramidon and aprotinin maximally inhibited ANP degradation, increasing its half-life from 0.42 to 15 minutes.

synapsesocial.com/papers/6a9bd8402072fd8addbb0ce9 https://doi.org/10.1042/bj2690801

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Respective roles of kallikrein and endopeptidase 24.11 in the metabolic pathway of atrial natriuretic peptide in the rat

Discussion

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Implication

Key Points

PICO

Cite This Study

Respective roles of kallikrein and endopeptidase 24.11 in the metabolic pathway of atrial natriuretic peptide in the rat

Discussion

Member takes

Implication

Key Points

PICO

Cite This Study

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