title: Hypolipidemic and antiatherosclerotic effects of a novel ACAT inhibitor, HL-004, in stroke-prone spontaneously hypertensive rats.
abstract: 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 administered 0.01-0.09% HL-004 mixed in a hypercholesterolemic (HC) diet for 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 mesenteric arteries, which is characteristic of SHRSP, was also decreased by HL-004. The ACAT activity of the small intestine and liver was decreased by HL-004. In particular, liver ACAT activity was significantly 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 that the ACAT inhibition in the intestine, liver, and aorta is involved in the hypolipidemic and antiatherosclerotic effects of HL-004.
authors: Medicinal Research Laboratories, Taisho Pharmaceutical Co. Ltd., Saitama, Japan.
authors: S
authors: S
authors: Murakami
authors: Y
authors: Y
authors: Nara
authors: Y
authors: Y
authors: Yamori
mesh_terms: D000083:Acetanilides / Q000494:pharmacology*; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002561:Cerebrovascular Disorders / Q000235:genetics; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004198:Disease Susceptibility; D004789:Enzyme Activation / Q000187:drug effects; D005223:Fats / Q000378:metabolism; D006949:Hyperlipidemias / Q000188:drug therapy*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000187:drug effects; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000083:Acetanilides; D000924:Anticholesteremic Agents; D005223:Fats; C092284:HL 004; D002784:Cholesterol; D002785:Sterol O-Acyltransferase