The regressive effect of an angiotensin II receptor blocker on formed fatty streaks in monkeys fed a high-cholesterol diet.
OBJECTIVE
To clarify the regressive effect of an angiotensin II type 1 receptor blocker (ARB) on already formed fatty streaks, we investigated the effect of the administration of an ARB, olmesartan, on formed fatty streaks in monkeys fed a high-cholesterol diet.


METHODS
After the monkeys were fed a high-cholesterol diet for 6 months, intimal hyperplasia was clearly observed on intravascular ultrasound. For the next 6 months, the high-cholesterol diet was continued, and olmesartan (3 mg/kg per day) or placebo was administered. A control group was fed a normal diet for 12 months.


RESULTS
Olmesartan did not significantly affect blood pressure or plasma cholesterol levels throughout the experiment. After 6 months of treatment with olmesartan, intimal hyperplasia was significantly lower than before treatment. Acetylcholine-induced relaxation in isolated carotid arteries was significantly less in the high-cholesterol diet placebo-treated group compared to the normal diet group, whereas its response was improved by olmesartan. Serum levels of monocyte chemoattractant protein were significantly increased with a high cholesterol load, but they were significantly suppressed by olmesartan.


CONCLUSIONS
We have demonstrated for the first time that an ARB, olmesartan, was found to have a regressive effect on formed fatty streaks in monkeys.
Takai
Shinji
S
Department of Pharmacology, Osaka Medical College, Takatsuki City, Osaka, Japan. pha010@art.osaka-med.ac.jp
Jin
Denan
D
Sakaguchi
Masato
M
Muramatsu
Michiko
M
Miyazaki
Mizuo
M
D000109:Acetylcholine / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D018932:Chemokine CCL2 / Q000097:blood; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D006965:Hyperplasia; D007093:Imidazoles / Q000627:therapeutic use; D066298:In Vitro Techniques; D008055:Lipids / Q000096:biosynthesis; D008252:Macaca fascicularis; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism; D011897:Random Allocation; D012083:Renin / Q000097:blood; D015203:Reproducibility of Results; D013777:Tetrazoles / Q000627:therapeutic use; D013997:Time Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D018084:Ultrasonography, Interventional / Q000379:methods; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D018932:Chemokine CCL2; D002791:Cholesterol, Dietary; D007093:Imidazoles; D008055:Lipids; D013777:Tetrazoles; D014665:Vasodilator Agents; C437965:olmesartan; D002784:Cholesterol; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D000109:Acetylcholine