Anti-atherosclerotic efficacy of olmesartan.
The possible inhibition of lipid deposition into vascular tissues by a novel angiotensin II type 1 receptor antagonist, olmesartan, was investigated in a primate high-cholesterol model. Twelve monkeys that were fed a high-cholesterol (4% cholesterol and 6% corn oil) diet for 6 months were divided into two groups: one group was given olmesartan medoxomil (10 mg/kg per day), and the other group was given no medication. A further control group of six monkeys was fed a normal diet throughout the study. The level of low-density lipoprotein (LDL) cholesterol was increased by the high-cholesterol diet, whereas that of high-density lipoprotein (HDL) cholesterol was decreased. Olmesartan decreased the areas of lipid deposition on the aortic surface and intimal cross-section area, but not the mean blood pressure and the levels of LDL and HDL cholesterol. The relaxation response of isolated carotid arteries to acetylcholine was suppressed in the high-cholesterol group, but this was improved by olmesartan. Olmesartan inhibited the accumulation of macrophages in the intimal layer. Serum levels of transforming growth factor (TGF)-beta1, macrophage colony-stimulating factor (M-CSF) and intracellular adhesion molecule (ICAM)-1 were increased in monkeys fed the high-cholesterol diet, but they were suppressed by olmesartan, although the decrease was not significant. Olmesartan reduced lipid deposition, accompanied by the improvement of vascular functions and the inhibition of macrophage accumulation in the intimal layer and showed a trend towards the suppression of serum TGF-beta1, M-CSF and ICAM-1.
Miyazaki
M
M
Department of Pharmacology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan. pha001@art.osaka-med.ac.jp
Takai
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D007093:Imidazoles / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007249:Inflammation / Q000097:blood; D008055:Lipids / Q000097:blood; D008252:Macaca fascicularis; D008297:Male; D000068557:Olmesartan Medoxomil; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D015415:Biomarkers; D002791:Cholesterol, Dietary; D007093:Imidazoles; D008055:Lipids; D013777:Tetrazoles; D000804:Angiotensin II; D000068557:Olmesartan Medoxomil; D002784:Cholesterol; D000109:Acetylcholine