In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 288, No. 2 ( 2005-02), p. H722-H728
Abstract:
Omapatrilat (OMP) is a novel mixed inhibitor of angiotensin-converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP), the enzyme that metabolizes natriuretic peptides. Congestive heart failure (CHF) is characterized by excessive sodium retention, attributed to both an excessive effect of angiotensin II and diminished responsiveness to natriuretic peptides. In this study, we examined the acute and chronic renal and cardiac effects of OMP in rats with compensated [urinary sodium excretion (U Na V) 〉 1,200 μeq/day] and decompensated (U Na V 〈 100 μeq/day) CHF, induced by a surgical aortocaval fistula (ACF). Bolus injection of OMP (10 mg/kg) to sham controls produced significant diuretic and natriuretic responses [U Na V increased from 0.67 ± 0.19 to 3.27 ± 1.35 μeq/min, P 〈 0.05; fractional sodium excretion (FE Na ) increased from 0.23 ± 0.06 to 0.95 ± 0.34%, P 〈 0.01] despite a significant decline in blood pressure (BP). Rats with compensated CHF displayed blunted diuresis and natriuresis to this dose of OMP but a significant decrease in BP. However, in rats with decompensated CHF, OMP induced significant natriuresis (FE Na increased from 0.18 ± 0.15 to 0.82 ± 0.26%, P 〈 0.05) despite a further decrease in BP (from 90 ± 9 to 71 ± 6 mmHg, P 〈 0.01). Two weeks after ACF, the heart/body weight ratio was significantly greater in rats with CHF than controls (0.51 ± 0.026 vs. 0.30 ± 0.004%, P 〈 0.0001), and U Na V was significantly lower. Immediate or late (1 or 6 days after ACF) OMP treatment in the drinking water (140 mg/l) reduced cardiac hypertrophy to 0.41–0.43% ( P 〈 0.01) and induced natriuresis. These results suggest that OMP improves both sodium balance and cardiac remodeling and might be advantageous to ACE inhibitors for the treatment of decompensated CHF.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.00737.2004
Language:
English
Publisher:
American Physiological Society
Publication Date:
2005
detail.hit.zdb_id:
1477308-9
SSG:
12
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