Acute natriuretic effect of fasidotrilat, a mixed inhibitor of neutral endopeptidase and angiotensin I-converting enzyme, in rats with heart failure.

Abstract

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.

• Authors: C Marie, C Mossiat, J M Lecomte, J Bralet
• Journal: Pharmacology (Pharmacology) Vol. 56 Issue 6 Pg. 291-6 (Jun 1998) ISSN: 0031-7012 [Print] Switzerland
• PMID: 9654215 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Enzyme Inhibitors
• aladotrilat
• Peptidyl-Dipeptidase A
• Neprilysin
• Alanine

Topics

• Alanine (analogs & derivatives, pharmacology, therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (pharmacology, therapeutic use)
• Animals
• Blood Pressure (drug effects, physiology)
• Diuresis (drug effects, physiology)
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Humans
• Hypertrophy, Right Ventricular (drug therapy, physiopathology)
• Ligation
• Male
• Myocardial Infarction (drug therapy, physiopathology)
• Natriuresis (drug effects, physiology)
• Neprilysin (antagonists & inhibitors)
• Peptidyl-Dipeptidase A (drug effects)
• Rats
• Rats, Wistar