ACUTE NATRIURETIC EFFECT OF FASIDOTRILAT, A MIXED INHIBITOR OF NEUTRAL ENDOPEPTIDASE AND ANGIOTENSIN-I-CONVERTING-ENZYME, IN RATS WITH HEART-FAILURE

The acute diuretic and natriuretic effects of fasidotrilat, a mixed in hibitor of neutral endopeptidase (NEP) and angiotensin I-converting en zyme (ACE) were evaluated in control and myocardial-infarcted rats. Fa sidotrilat injection (10 mg/kg i.v.) had no significant effect on arte rial blood pressure and led to significant elevations in urine volume (+57% in control rats and +114% in infarcted rats) and of urinary sodi um excretion (+81% in control rats and +225% in infarcted rats). Compa rison between control and infarcted rats showed that fasidotrilat-indu ced changes in diuresis and natriuresis were higher in infarcted rats (2.4-fold for diuresis and 4.7-fold for natriuresis, p < 0.05), despit e a lower perfusion pressure (-10 mm Hg) in infarcted rats. These data show the potential therapeutic interest of mixed NEP/ACE inhibitors i n congestive heart failure.