Comparative Effects of Candesartan and Amlodipine in a Monkey Atherosclerotic Model

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 Angiotensin II has been shown to be a potent vasoconstrictor, and it also promotes vascular proliferation via induction of several growth factors and cytokines (4, 5). We previously reported that ACE activity in atherosclerotic lesions in monkeys fed a high-cholesterol diet was increased significantly compared with that in normal lesions (6,7). In this atherosclerotic model, an ACE inhibitor or an angiotensin II receptor blocker (ARB) significantly reduced the progression of atherosclerosis beyond reduction of blood pressure and plasma cholesterol levels (6-8). The mechanism of angiotensin II in the development of atherosclerosis is thought to be various angiotensin II-induced actions such as the induction of growth factors, inflammatory cytokines, adhesion

Regression of Atherosclerosis by Amlodipine via Anti-Inflammatory and Anti-Oxidative Stress Actions

“…They reported that in the ApoEKO mice treated with streptozotocin, the vascular renin-angiotensin system plays a critical role in mediating acceleration of ath- erosclerosis, and this may explain why irbesartan was superior to amlodipine in reducing the diabetes-associated acceleration of atherosclerosis. Takai et al (23) reported that amlodipine tended to decrease the atherosclerotic area in monkeys fed a high-cholesterol diet, although this effect was not statistically significant. In contrast, others have reported that amlodipine inhibited atherosclerosis in non-diabetic animal models of atherosclerosis (24,25).…”

Protective Effects of an Angiotensin II Receptor Blocker and a Long-Acting Calcium Channel Blocker against Cardiovascular Organ Injuries in Hypertensive Patients

“…In particular, angiotensin II promotes hypertrophy of cardiovascular cells and aldosterone causes fibrosis of the cardiovascular tissues (12,13). Therefore, antihypertensive drugs that suppress RAAS, such as ARBs and ACE inhibitors, are expected to confer protection against hypertensive injuries in cardiovascular organs that goes beyond their hypotensive effects (32). Fibrosis and deposition of intercellular matrices such as collagen in the cardiac tissue cause reduction in left ventricular distensibility (33).…”

Increased Transient Receptor Potential Canonical Type 3 Channels in Vasculature From Hypertensive Rats

“…The AT1 receptor antagonists irbesartan and candesartan but not amlodipine treatment showed beneficial effects in diabetic apolipoprotein E-null mouse or monkeys. [31][32] …”