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: S Murakami, Y Nara, Y Yamori
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 63 Issue 1 Pg. 23-32 (Aug 1995) ISSN: 0014-4800 [Print] Netherlands
• PMID: 8759051 (Publication Type: Journal Article)

Chemical References

• Acetanilides
• Anticholesteremic Agents
• Fats
• HL 004
• Cholesterol
• Sterol O-Acyltransferase

Topics

• Acetanilides (pharmacology)
• Animals
• Anticholesteremic Agents (therapeutic use)
• Cerebrovascular Disorders (genetics)
• Cholesterol (blood, metabolism)
• Disease Susceptibility
• Enzyme Activation (drug effects)
• Fats (metabolism)
• Hyperlipidemias (drug therapy)
• Male
• Rats
• Rats, Inbred SHR
• Sterol O-Acyltransferase (antagonists & inhibitors, drug effects)
• Tissue Distribution (drug effects)