Why the study?
Does fasidotrilat injection increase diuresis and natriuresis in myocardial-infarcted rats compared to control rats?
Does fasidotrilat injection increase diuresis and natriuresis in myocardial-infarcted rats compared to control rats?
Fasidotrilat, a mixed NEP/ACE inhibitor, produces a greater acute diuretic and natriuretic effect in rats with heart failure compared to healthy controls, suggesting potential therapeutic value.
Suggests enhanced dual NEP/ACE inhibition effects in experimental HF; hypothesis-generating and leaves open clinical translation.
The acute diuretic and natriuretic effects of fasidotrilat, a mixed inhibitor of neutral endopeptidase (NEP) and angiotensin I-converting enzyme (ACE) were evaluated in control and myocardial-infarcted rats. Fasidotrilat injection (10 mg/kg i.v.) had no significant effect on arterial blood pressure and led to significant elevations in urine volume (+57% in control rats and +114% in infarcted rats) and of urinary sodium excretion (+81% in control rats and +225% in infarcted rats). Comparison between control and infarcted rats showed that fasidotrilat-induced changes in diuresis and natriuresis were higher in infarcted rats (2.4-fold for diuresis and 4.7-fold for natriuresis, p < 0.05), despite a lower perfusion pressure (-10 mm Hg) in infarcted rats. These data show the potential therapeutic interest of mixed NEP/ACE inhibitors in congestive heart failure.
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Marie et al. (1998) studied this question.
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