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Comparative effects of candesartan and amlodipine in a monkey atherosclerotic model
Shinji Takai1, Denan Jin, Masato Sakaguchi
1Department of Pharmacology, Osaka Medical College, Takatsuki, Japan. Pha010@art.osaka-med.ac.jp
Abstract:
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.
Insights
Angiotensin II receptor blockers, like candesartan, significantly reduced atherosclerosis in monkeys. This effect appears independent of blood pressure reduction, suggesting a direct role in preventing arterial disease.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Atherosclerosis Research
Background:
- Angiotensin II receptor blockers (ARBs) show potential in preventing atherosclerosis beyond blood pressure reduction.
- The specific role of hypotensive effects in primate atherosclerosis remains unclear.
Purpose of the Study:
- To investigate if antihypertensive agents, candesartan (ARB) and amlodipine (calcium channel blocker), prevent atherosclerotic lesions in the aorta of high-cholesterol-fed monkeys.
- To differentiate the effects of angiotensin II blockade versus blood pressure reduction on atherosclerosis.
Main Methods:
- Monkeys were fed a high-cholesterol diet for six months.
- Treatment groups included a control, candesartan (1 mg/kg/day), and amlodipine (5 mg/kg/day).
- Systolic blood pressure, serum cholesterol, and aortic atherosclerotic area were measured. Angiotensin-converting enzyme activity was assessed in plasma and aorta.
Main Results:
- Both candesartan and amlodipine reduced systolic blood pressure by approximately 20 mmHg without altering serum cholesterol.
- Candesartan significantly decreased the ratio of atherosclerotic area to total area in the thoracic aorta.
- Amlodipine showed a trend towards decreasing this ratio. Candesartan, but not amlodipine, reduced aortic angiotensin-converting enzyme activity.
Conclusions:
- Blockade of angiotensin II action, rather than its hypotensive effect, appears crucial in preventing atherosclerosis development in primates.
- Candesartan demonstrates significant anti-atherosclerotic properties in this primate model.
- Further research into the mechanisms of ARBs in cardiovascular disease prevention is warranted.
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