Eplerenone inhibits atherosclerosis in nonhuman primates.
Aldosterone may be involved in the pathogenesis of atherosclerosis. We investigated the effect of eplerenone, a selective mineralocorticoid receptor blocker, on atherosclerosis in monkeys fed a high-cholesterol diet. Monkeys fed a high-cholesterol diet for 9 months were divided into 3 groups: those treated with a low dose of eplerenone (30 mg/kg per day); those treated with a high dose of eplerenone (60 mg/kg per day); and the placebo-treated group. The normal group consisted of monkeys fed a normal diet. There were no significant differences in blood pressure and cholesterol levels between the placebo- and eplerenone-treated groups. On the other hand, monocyte chemoattractant protein-1 and malondialdehyde-modified LDL were significantly higher in the placebo-treated group than in the normal group, whereas they were suppressed in the eplerenone-treated groups. The ratio of intimal volume to total volume by intravascular ultrasound analysis imaging of the aortas was dose-dependently lower in the eplerenone-treated groups than in the placebo-treated group. Acetylcholine-induced vasorelaxation was significantly weaker in the placebo-treated group than in the normal group, but the vasorelaxation was strengthened in the eplerenone-treated groups. A significant upregulation of angiotensin-converting enzyme activity was observed in the placebo-treated group, but the activity was suppressed in the eplerenone-treated groups. In conclusion, eplerenone may strengthen the endothelium-dependent relaxation and suppress angiotensin-converting enzyme activity in the vasculature, thus preventing the development of atherosclerosis in nonhuman primates.
Takai
Shinji
S
Department of Pharmacology, Osaka Medical College, Takatsuki City, Osaka 569-8686, Japan. pha010@art.osaka-med.ac.jp
Jin
Denan
D
Muramatsu
Michiko
M
Kirimura
Kazuyoshi
K
Sakonjo
Hiroshi
H
Miyazaki
Mizuo
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000201:enzymology / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects; D018932:Chemokine CCL2 / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D000077545:Eplerenone; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008252:Macaca fascicularis; D008297:Male; D008315:Malondialdehyde / Q000031:analogs & derivatives / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012083:Renin / Q000097:blood; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000187:drug effects; D014463:Ultrasonography; D014664:Vasodilation
D018932:Chemokine CCL2; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; C502964:malondialdehyde-low density lipoprotein, mouse; D013148:Spironolactone; D008315:Malondialdehyde; D000077545:Eplerenone; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D000109:Acetylcholine