What question did this study set out to answer?

Investigate whether inhibiting neutral endopeptidase amplifies the physiological actions of endogenous atrial natriuretic peptide on blood pressure and fluid distribution.

January 1, 1992American Journal of HypertensionOpen Access

Inhibition of Neutral Endopeptidase Amplifies the Effects of Endogenous Atrial Natriuretic Peptide on Blood Pressure and Fluid Partition

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Population

Anesthetized, bilaterally nephrectomized Sprague-Dawley rats

Comparison

SQ 28,603 30 mg/kg intravenously over 45 min… vs Vehicle alone

Design

Preclinical

Authors

JVJean‐Pierre ValentinElectrophysiology CQChangbin QiuActelion (Switzerland)EWEckehart WiedemannBronx-Lebanon Hospital Center

Discussion

Member takes

Implication

Animal data preclude practice change; hypothesis-generating for NEP inhibition to potentiate endogenous ANP in hypertension research.

Key Points

Investigate whether inhibiting neutral endopeptidase amplifies the physiological actions of endogenous atrial natriuretic peptide on blood pressure and fluid distribution.
Administered the neutral endopeptidase inhibitor SQ 28,603 (30 mg/kg IV over 45 minutes) or vehicle to anesthetized, bilaterally nephrectomized Sprague-Dawley rats.
Evaluated the dependence on endogenous atrial natriuretic peptide by administering SQ 28,603 to rats pretreated with rabbit antirat ANP antiserum.
SQ 28,603 infusion decreased mean arterial pressure by 3.2 ± 0.5% and increased hematocrit by 4.9 ± 0.5%, contrasting with vehicle controls which exhibited a 3.2 ± 2.2% increase in pressure and a 0.9 ± 0.7% rise in hematocrit.
Plasma protein concentration rose by 2.5 ± 0.4% following SQ 28,603 administration, indicating increased vascular permeability to fluid and protein.
Pretreatment with ANP antiserum reversed the response to SQ 28,603, resulting in a 3.8 ± 0.5% rise in blood pressure and a 1.0 ± 0.4% increase in hematocrit.

Structured PICO

Population

Anesthetized, bilaterally nephrectomized Sprague-Dawley rats

Intervention

SQ 28,603 (neutral endopeptidase inhibitor) 30 mg/kg intravenously over 45 min, with or without pretreatment with rabbit antirat ANP antiserum

Comparator

Vehicle alone

Outcome

Changes in mean arterial blood pressure (MAP) and hematocrit (Hct)surrogate

Inhibition of neutral endopeptidase with SQ 28,603 amplifies the actions of endogenous ANP on blood pressure and fluid partition in a rat model.

Cite This Study

Valentin et al. (1992) studied this question.

synapsesocial.com/papers/6a901c2ac7b7d4543f89d50f https://doi.org/10.1093/ajh/5.2.88

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Inhibition of Neutral Endopeptidase Amplifies the Effects of Endogenous Atrial Natriuretic Peptide on Blood Pressure and Fluid Partition

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Inhibition of Neutral Endopeptidase Amplifies the Effects of Endogenous Atrial Natriuretic Peptide on Blood Pressure and Fluid Partition

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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