HYPOLIPIDEMIC AND ANTIATHEROSCLEROTIC EFFECTS OF A NOVEL ACAT INHIBITOR, HL-004, IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

The hypolipidemic and antiatherosclerotic effects of a novel acyl CoA: cholesterol acyltransferase (ACAT) inhibitor, HL-004, were studied in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were admi nistered 0.01-0.09% HL-004 mixed in a hypercholesterolemic (HC) diet f or 50 days. HL-004 reduced the cholesterol and triglyceride levels in serum, as well as those in the liver, small intestine, and aorta, in a dose-dependent manner. HC diet-induced severe fat deposition in the m esenteric arteries, which is characteristic of SHRSP, was also decreas ed by HL-004. The ACAT activity of the small intestine and liver was d ecreased by HL-004. In particular, liver ACAT activity was significant ly low in SHRSP given 0.09% HL-004, compared to that of normal animals . These results suggest that HL-004 is a systemic ACAT inhibitor and t hat the ACAT inhibition in the intestine, liver, and aorta is involved in the hypolipidemic and antiatherosclerotic effects of HL-004. (C) 1 995 Academic Press, Inc.