| Abstract: | Atherosclerotic lesions were formed in the aorta of rats given a high cholesterol diet containing propylthiouracil (PTU) and vitamin D2 (atherogenic diet) for 8 weeks. The effects of niceritrol (pentaerythritol tetranicotinate), which lower the plasma lipid level, on lipid metabolism in the arterial wall of the atherosclerotic rats were studied. Niceritrol significantly decreased the plasma cholesterol level of atherosclerotic rats, which was 823 mg/100 ml, or about ten times that of control rats. On treatment with niceritrol, the cholesterol level was reduced most in the very low density lipoprotein (VLDL) fraction (d less than 1.006). Heparin-releasable lipoprotein lipase activity in epididymal adipose tissue, lipoprotein lipase activity in post-heparin plasma, and VLDL-triolein hydrolyzing activity in adipose tissue stromal vessels were all higher in niceritrol-treated atherosclerotic rats. Of the enzymes in the arterial wall concerned with cholesterol ester metabolism, acid cholesterol esterase activity was decreased in atherosclerotic rats, while niceritrol treatment increased this activity. The ratio of acyl-CoA cholesterol acyltransferase activity (ACAT) to neutral cholesterol esterase activity was higher in atherosclerotic rats than in control rats, but was lower in niceritrol-treated rats than in atherosclerotic rats. From these results, it is concluded that niceritrol modifies enzyme activities in such a way as to reduce the cholesterol ester content of the arterial wall and lower plasma VLDL and LDL cholesterol levels. |
