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Abstract
Angiotensin-converting enzyme (ACE) is mainly responsible for converting angiotensin
I (AI) to angiotensin II (AII), and ACE inhibitors prevent atherosclerosis in animal
models. Neutral endopeptidase 24.11 (NEP) degrades substance P, kinins and atrial
natriuretic peptide (ANP), and aortic wall NEP activity was found to be increased
in atherosclerosis. In the present study, we have evaluated the effect of candoxatril,
a NEP inhibitor, and of omapatrilat, a dual ACE and NEP inhibitor, on the development
of fatty streak in apolipoprotein E (apoE)-deficient mice. Groups of ten male apoE-deficient
mice were given either placebo, candoxatril 50 mg/kg per day, or omapatrilat 10, or
100 mg/kg per day for 4 months. None of the treatments influenced body weight, serum
total or HDL-cholesterol. Compared with the placebo, candoxatril did not protect the
mice from fatty streak deposit. In contrast, omapatrilat dose dependently inhibited
the constitution of fatty streak in apoE-deficient mice. The precise advantages of
the dual ACE and NEP inhibition versus the inhibition of only ACE should now be considered
in the prevention of atherosclerosis as well as in the occurrence of its complications.