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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2601-2608.)
© 1997 American Heart Association, Inc.

Articles

Antiatherogenic Effects of a Novel Lipoprotein Lipase-Enhancing Agent in Cholesterol-Fed New Zealand White Rabbits

Tsuyoshi Chiba; Shinji Miura; Fusae Sawamura; Reiko Uetsuka; Isao Tomita; Yasuhide Inoue; Kazuhiko Tsutsumi; ; Takako Tomita

From the School of Pharmaceutical Sciences (T.C., S.M., F.S., R.U., I.T.) and Graduate School of Health Sciences (T.T.), University of Shizuoka, Shizuoka, and New Drug Research Laboratory, Naruto Research Institute, Otsuka Pharmaceutical Factory (Y.I., K.T.), Tokushima, Japan.

Correspondence to Dr Takako Tomita, Graduate School of Health Sciences, University of Shizuoka, 52-1 Yada, Shizuoka, Japan 422. Email tomitat{at}sea.u-shizuoka-ken.ac.jp

Abstract Following our report that administration of 4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl) benzamide (NO-1886) to rats elevated postheparin lipoprotein lipase (LPL) activity through an increase in the enzyme mass, we now investigate antiatherogenic effects of NO-1886 in cholesterol-fed New Zealand White rabbits. For 20 weeks, four groups of male rabbits received regular rabbit chow (the normal control), 0.25% cholesterol-containing chow (the control), and cholesterol chow supplemented with 0.5% and 1.0% NO-1886, respectively. Postheparin LPL activity at week 10 was raised by 30% in 0.5% of the NO-1886 group and 40% in 1.0% of the NO-1886 group compared with those in the control. The area under the curve of plasma cholesterol level was not different in three cholesterol-fed groups whereas the area under the curve of HDL cholesterol was approximately twofold greater in the two NO- 1886 groups than in the control, and the area under the curve of plasma triglyceride was reduced to the level of the normal control. LPL activity was correlated with HDL cholesterol (r=.764, n=18) and triglyceride (r=-.627, n=18). Relative atheromatous area, aortic cholesterol, and triglyceride contents were reduced to approximately 25%, 60%, and 55%, respectively, of the control values by NO-1886 ingestion. Multiple regression analysis of LPL, HDL cholesterol, and triglyceride indicated that HDL cholesterol was the most powerful protector against aortic cholesterol accumulation, and triglyceride was the one to protect against the atheromatous area. We concluded that NO-1886 prevented the development of atherosclerosis through increasing LPL activity with a consequent increase in HDL cholesterol and a decrease in triglyceride without a significant influence of plasma cholesterol level.

Key Words: lipoprotein lipase • high density lipoprotein • NO-1886 • New Zealand White rabbit • antiatherogenic effects

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