Volume 2, Number 1, March 2001

Prevention of atherosclerosis by specific AT₁-receptor blockade with candesartan cilexetil
Vasilios Papademetriou, Philippe Mammillot, Robert Redman, Aldo Notargiacomo, Puneet Narayan, Raj Lakshman

Several studies indicate that blockade of the renin-angiotensin-aldosterone system (RAAS) can prevent atherosclerosis and vascular events, but the precise mechanisms involved are still unclear. In this study, we investigated the effect of the AT₁-receptor blocker, candesartan, in the prevention of atherosclerosis in Watanabe heritable hyperlipidaemic (WHHL) rabbits and also the effect of AT₁-receptor blockade in the uptake of oxidised LDL by macrophage cell cultures.
In the first set of experiments, 12 WHHL rabbits were randomly assigned to three groups: placebo, atenolol 5 mg/kg daily or candesartan 2 mg/kg daily for six months. Compared with controls and atenolol-treated rabbits, candesartan treatment resulted in a significant 50–60% reduction of atherosclerotic plaque formation and a 66% reduction in cholesterol accumulation in the thoracic aorta.
Studies in macrophage cultures indicated that candesartan prevented uptake of oxidised LDL-(oxLDL)-cholesterol by cultured macrophages. Candesartan inhibited the uptake of oxLDL in a dose-dependent manner, reaching a maximum inhibition of 70% at concentrations of 5.6 μg/ml. Further studies in other animal models and well-designed trials in humans are warranted to further explore the role of AT₁-receptor blockade in the prevention of atherosclerosis.

JRAAS 2001;2:77-80.

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