Abstract
Omapatrilat inhibits both angiotensin-converting enzyme
(ACE) and neutral endopeptidase (NEP). ACE inhibitors
have been shown to inhibit atherosclerosis in
apoE-deficient mice and in several other animal models
but failed in low-density lipoprotein (LDL) receptor–
deficient mice despite effective inhibition of the reninangiotensin-
aldosterone system. The aim of the present
study was to examine the effect of omapatrilat on atherogenesis
in diabetic and nondiabetic LDL receptor–deficient
mice. LDL receptor–deficient male mice were randomly
divided into 4 groups (n = 11 each). Diabetes was induced
in 2 groups by low-dose STZ, the other 2 groups served
as nondiabetic controls. Omapatrilat (70 mg/kg/day)
was administered to one of the diabetic and to one of
the nondiabetic groups. The diabetic and the nondiabetic
mice were sacrificed after 3 and 5 weeks, respectively.
The aortae were examined and the atherosclerotic
plaque area was measured. The atherosclerotic plaque
area was significantly smaller in the omapatrilat-treated
mice, both diabetic and nondiabetic, as compared to nontreated
controls. The mean plaque area of omapatrilattreated
nondiabetic mice was 9357 ± 7293 μ