Key result
Neutral endopeptidase inhibition with SCH 39370 in sheep with heart failure significantly increased plasma ANP from 328 to 570 pmol/L (p<0.001) and decreased left atrial pressure.
Why the study?
Does neutral endopeptidase inhibition with SCH 39370 improve hemodynamic and hormonal parameters in an ovine model of heart failure?
Does neutral endopeptidase inhibition with SCH 39370 improve hemodynamic and hormonal parameters in an ovine model of heart failure?
Neutral endopeptidase inhibition with SCH 39370 acutely increases ANP and cyclic GMP levels, promotes natriuresis, and reduces left atrial pressure in an ovine model of pacing-induced heart failure.
Answers are grounded in this paper and cite their sources.
Does not support clinical adoption in HF; leaves open translation of ovine ANP augmentation to human therapy.
The effects of neutral endopeptidase inhibition (NEP-I) were studied in 6 conscious sheep with heart failure (HF) induced by rapid ventricular pacing for 7 days. Measurements were performed 1 h before and for 6 h after intravenous (i.v.) bolus administration of vehicle and SCH 39370 (1.25 and 5 mg/kg) on separate days. After the higher dose, an index of serum NEP activity decreased from 0.83 +/- 0.05 to 0.13 +/- 0.07 nmol/ml/min (p less than 0.001) at 1 h and then returned to control levels at 6 h. Plasma atrial natriuretic peptide (ANP) and cyclic GMP rose from 328 +/- 28 and 20.2 +/- 4.3 to a peak of 570 +/- 65 pmol/L (p less than 0.001) and 28.7 +/- 6.3 nmol/L (p less than 0.05) respectively. Natriuresis and diuresis were significant and left atrial pressure (LAP) decreased from 21.9 +/- 1.1 to 20.1 +/- 0.8 mm Hg (p less than 0.05). Despite high endogenous ANP levels in HF, NEP-I further increases both ANP and its "second messenger." Its natriuretic and hemodynamic effects are consistent with enhanced ANP activity in renal and vascular tissues, suggesting that NEP-I may be useful for treating HF.
No takes yet. Share an insight, caveat, or question.
Fitzpatrick et al. (1992) studied Heart failure (n=6). SCH 39370 (neutral endopeptidase inhibition) vs. Vehicle was evaluated on Plasma atrial natriuretic peptide (ANP) (p=<0.001). Neutral endopeptidase inhibition with SCH 39370 in sheep with heart failure significantly increased plasma ANP from 328 to 570 pmol/L (p<0.001) and decreased left atrial pressure.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: