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)benzamid e, 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.
The First Department of Internal Medicine, Aichi Medical University, Japan.
T
T
Hara
M
M
Kusunoki
K
K
Tsutsumi
K
K
Okada
S
S
Sakamoto
M
M
Ohnaka
T
T
Nakamura
T
T
Miyata
K
K
Nakayama
A
A
Fukatsu
K
K
Kato
S
S
Kakumu
Y
Y
Nakaya
D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta; D001161:Arteriosclerosis / Q000503:physiopathology; D001549:Benzamides / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D004789:Enzyme Activation; D007328:Insulin / Q000097:blood; D008054:Lipid Peroxides / Q000097:blood; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D001549:Benzamides; D001786:Blood Glucose; D007328:Insulin; D008054:Lipid Peroxides; D008055:Lipids; D009943:Organophosphorus Compounds; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide; D013482:Superoxide Dismutase; D008071:Lipoprotein Lipase