Original Article: PDF OnlyAcute Hemodynamic, Hormonal, and Renal Effects of Neutral Endopeptidase Inhibition in Ovine Heart FailureFitzpatrick, M. A.; Rademaker, M. T.; Charles, C. J.; Yandle, T. G.; Espiner, E. A.; Ikram, H.; Sybertz, E.Author Information Departments of Cardiology and Endocrinology, The Princess Margaret Hospital, Christchurch, New Zealand; and Schering-Plough Research, Bloomfield, New Jersey, U.S.A. Journal of Cardiovascular Pharmacology: April 1992 - Volume 19 - Issue 4 - p 635-640 Free Abstract 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 < 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 < 0.001) and 28.7 ± 6.3 nmol/L (p < 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 < 0.05). Despite high endogenous ANP levels in HF, NEP-I further increases both ANP and its “second messenger.” Its natriuretic and hemodyniamic effects are consistent with enhanced ANP activity in renal and vascular tissues, suggesting that NEP-I may be useful for treating HF. © Lippincott-Raven Publishers.