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October 1, 1989Proceedings of the National Academy of SciencesOpen Access

Protection of atrial natriuretic factor against degradation: diuretic and natriuretic responses after in vivo inhibition of enkephalinase (EC 3.4.24.11) by acetorphan.

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Why the study?

Does acetorphan increase endogenous atrial natriuretic factor (ANF) levels and induce diuresis and natriuresis in healthy humans?

Population

Mice and 8 healthy human volunteers

Comparison

Acetorphan (oral administration in humans) vs Placebo

Design

RCT, Randomized, Double-blind, placebo-controlled

Authors

CGClaude P. GrosCentre National de la Recherche ScientifiqueASAnny SouqueInsermJSJ. SchwartzBioprojet (France)

Discussion

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Implication

Supports neprilysin inhibition to augment ANF effects; extends proof-of-concept from healthy volunteers toward heart failure trials.

Structured PICO

Does acetorphan increase endogenous atrial natriuretic factor (ANF) levels and induce diuresis and natriuresis in healthy humans?

P
Population
Mice and 8 healthy human volunteers
I
Intervention
Acetorphan (oral administration in humans)
C
Comparator
Placebo
O
Outcome
Plasma ANF-like immunoreactivity, urinary volume, and sodium excretionsurrogate

Inhibition of enkephalinase by acetorphan prevents the degradation of atrial natriuretic factor, leading to increased circulating levels, diuresis, and natriuresis, providing early proof-of-concept for neprilysin inhibition in cardiovascular disease.

Cite This Study

Gros et al. (1989) studied this question.

synapsesocial.com/papers/6a7209c3f44fa9f079dfa70ehttps://doi.org/10.1073/pnas.86.19.7580
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Clearance and early hydrolysis of atrial natriuretic factor in vivo. Structural analysis of cleavage sites and design of an analogue that inhibits hormone cleavage.1988 · 35 citations
  2. 2Binding and functional effects of atrial natriuretic factor in isolated rat kidney1987 · 19 citations
  3. 3Specific membrane receptors for atrial natriuretic factor in renal and vascular tissues.1984 · 262 citations
  4. 4Atrial Natriuretic Factor: A Hormone Produced by the Heart1985 · 989 citations
  5. 5The Heart and the Atrial Natriuretic Factor*1985 · 753 citations