Mechanisms of angiotensin II type 1 receptor blocker for anti-atherosclerotic effect in monkeys fed a high-cholesterol diet.
OBJECTIVE To clarify the mechanism of the anti-atherosclerotic effect of angiotensin II type 1 receptor blocker (ARB) in primates, we investigated whether an ARB (CS-866) affects the serum markers of inflammation and growth factors, and the endothelial function in monkeys fed a high-cholesterol diet. DESIGN Monkeys fed a high-cholesterol diet for 6 months were divided into two groups: one group was given an ARB, CS-866 (10 mg/kg per day), and the other group was not. The control group was fed a normal diet. RESULTS Blood pressure and the plasma cholesterol level were not affected by CS-866. Plasma levels of angiotensin II, renin, angiotensin converting enzyme and chymase were not changed by the high-cholesterol diet, whereas vascular angiotensin converting enzyme, but not chymase, was significantly increased. Serum levels of macrophage-colony stimulating factor, transforming growth factor-beta1 and intracellular adhesion molecule-1 were significantly increased in monkeys fed a high-cholesterol diet but they were suppressed by CS-866. The relaxation response of isolated carotid arteries to acetylcholine was suppressed in the high-cholesterol group, whereas it was improved by CS-866. CONCLUSIONS CS-866 reduced lipid deposition along with the suppression of serum macrophage-colony stimulating factor, transforming growth factor-beta 1 and intracellular adhesion molecule-1, and the improvement of vascular functions, suggesting that ARB has multiple mechanisms for reducing lipid deposition in primates.
Takai
Shinji
S
Department of Pharmacology, Osaka Medical College, Takatsuki City, Osaka, Japan. Pha010@art.osaka-med.ac.jp
Kim
Shokei
S
Sakonjo
Hiroshi
H
Miyazaki
Mizuo
M
D000109:Acetylcholine / Q000008:administration & dosage; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D001161:Arteriosclerosis / Q000473:pathology / Q000517:prevention & control*; D002339:Carotid Arteries / Q000503:physiopathology; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D053818:Chymases; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008055:Lipids / Q000097:blood; D008252:Macaca fascicularis; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood; D008297:Male; D000068557:Olmesartan Medoxomil; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D012697:Serine Endopeptidases / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014664:Vasodilation
D057911:Angiotensin Receptor Antagonists; D002791:Cholesterol, Dietary; D007093:Imidazoles; D008055:Lipids; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D018799:Intercellular Adhesion Molecule-1; D000068557:Olmesartan Medoxomil; D016173:Macrophage Colony-Stimulating Factor; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases; D000109:Acetylcholine