A lipoprotein lipase activator, NO-1886, improves endothelium-dependent relaxation of rat aorta associated with aging

Endothelial function is closely related to development of atherosclerosis and is impaired with aging. The novel compound NO-1886, 4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide, is a lipoprotein lipase activator and its long term administration protects against the development of experimental atherosclerosis in animals. The aim of this study was to ascertain whether NO-1886 ameliorates the impaired endothelium-dependent relaxation of rat aorta associated with aging. NO-1886 (50 mg/kg p.o.) was administered to 7-month old rats for 3 months. Plasma lipid, glucose and insulin levels in old control rats (10 months of age) were significantly higher than those of young rats (2 months of age). NO-1886 decreased plasma triglyceride levels (old rats, 233±10 mg/dl; old rats+NO-1886, 172±16 mg/dl, P<0.01) and increased plasma high density lipoprotein (HDL) cholesterol level (old rats, 72±6 mg/dl; old rats+NO-1886, 142±6 mg/dl, P<0.001) in old rats, but had no effects on plasma glucose or insulin. The endothelium-dependent relaxation of the thoracic aorta caused by histamine was significantly impaired in old rats (% relaxation at 10−5.5 M histamine: young rats 25.4±3.1%; old rats 14.1±1.9%, P<0.01), an effect completely prevented by NO-1886 (old rats+NO-1886; 22.8±2.8%, P<0.05 vs. old rats). In contrast, NO-1886 showed no effect on the endothelium-independent relaxation by sodium nitroprusside. These results indicate that NO-1886 improves impaired endothelium-dependent relaxation of rat aorta associated with aging, possibly by correcting lipid metabolism.