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July 1, 1994AJP Heart and Circulatory Physiology

Role of endogenous atrial natriuretic peptide on systemic and renal hemodynamics in heart failure rats

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Why the study?

Does ANP-receptor antagonism with HS-142-1 alter systemic and renal hemodynamics in rats with heart failure?

Population

Rats with surgically induced myocardial infarction (heart failure model) and sham-operated control rats

Comparison

HS-142-1, a nonpeptide ANP-receptor antagonist vs Sham-operated rats and pre-administration baseline

Design

Preclinical

Key result

Administration of the ANP-receptor antagonist HS-142-1 in heart failure rats significantly reduced plasma cGMP (10.6 vs 2.7 nM, P<0.05) and decreased urine flow and sodium excretion.

Authors

TNToshio NishikimiKMKatsuyuki MiuraNMNaoto Minamino

Discussion

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Overview

Supports ANP-mediated renal compensation in experimental HF; leaves open human translation and therapeutic implications.

Structured PICO

Does ANP-receptor antagonism with HS-142-1 alter systemic and renal hemodynamics in rats with heart failure?

P
Population
Rats with surgically induced myocardial infarction (heart failure) and sham-operated controls.
I
Intervention
HS-142-1 (HS; 3 mg/kg body wt iv), a nonpeptide ANP-receptor antagonist
C
Comparator
Sham-operated rats and pre-administration baseline
O
Outcome
Systemic and renal hemodynamics, plasma and urinary cGMP levels, urine flow, and urinary sodium excretionsurrogate

Main Result

Absolute Event Rate: 2.7% vs 10.6%

p-value: p=<0.05

Endogenous ANP in heart failure compensates primarily via diuresis and natriuresis through inhibition of renal tubular reabsorption, rather than by directly maintaining systemic hemodynamics.

Cite This Study

Nishikimi et al. (1994) studied Heart failure. HS-142-1 vs. Baseline/Sham-operated rats was evaluated on Plasma concentration of guanosine 3',5'-cyclic monophosphate (p=<0.05). Administration of the ANP-receptor antagonist HS-142-1 in heart failure rats significantly reduced plasma cGMP (10.6 vs 2.7 nM, P<0.05) and decreased urine flow and sodium excretion.

synapsesocial.com/papers/6a1ec4adbf2a5d44faaf4be7https://doi.org/10.1152/ajpheart.1994.267.1.h182
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