Comparative effects of candesartan and amlodipine in a monkey atherosclerotic model.
Angiotensin II receptor blockers could prevent the development of atherosclerosis beyond reducing blood pressure in monkeys fed a high-cholesterol diet. However, it has been unclear whether hypotensive effects improve atherosclerosis in primates. We investigated whether antihypertensive agents, an angiotensin II receptor antagonist, candesartan, and a calcium channel blocker, amlodipine, prevent areas of atherosclerotic lesions in the aorta of monkeys fed a high-cholesterol diet. Seventeen male monkeys fed a high-cholesterol diet for 6 months were grouped as follows: a high-cholesterol diet group (n=5), a candesartan-treated group (1 mg/kg per day, n=6) and an amlodipine-treated group (5 mg/kg per day, n=6). Candesartan and amlodipine showed a similar hypotensive effect by decreasing the systolic blood pressure approximately 20 mmHg, while these agents did not affect serum cholesterol levels. The ratio of atherosclerotic area to total area in thoracic aorta was significantly decreased by treatment with candesartan, but the ratio tended to be decreased by treatment with amlodipine. Although the angiotensin-converting enzyme activity in plasma was not changed by treatment with candesartan or amlodipine, the angiotensin-converting enzyme activity in the thoracic aorta was obviously reduced by treatment with candesartan, but not with amlodipine. Therefore, a blockade of angiotensin II action rather than a hypotensive effect may play an important role in preventing the development of atherosclerosis in primates.
Department of Pharmacology, Osaka Medical College, Takatsuki, Japan. Pha010@art.osaka-med.ac.jp
Shinji
S
Takai
Denan
D
Jin
Masato
M
Sakaguchi
Michiko
M
Muramatsu
Kenji
K
Ishii
Kazuyoshi
K
Kirimura
Hiroshi
H
Sakonjo
Mizuo
M
Miyazaki
D017311:Amlodipine / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000037:antagonists & inhibitors*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001018:Aortic Diseases / Q000473:pathology / Q000517:prevention & control*; D001161:Arteriosclerosis / Q000473:pathology / Q000517:prevention & control*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D002791:Cholesterol, Dietary; D013777:Tetrazoles; D017311:Amlodipine; D002784:Cholesterol; D007703:Peptidyl-Dipeptidase A; D012083:Renin; C081643:candesartan