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Journal of Renin-Angiotensin-Aldosterone System
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Prevention of atherosclerosis by specific AT1-receptor blockade with candesartan cilexetil

Vasilios Papademetriou

The Va Medical Center and Georgetown University and the George Washington University Washington D.C. USA, papavip@ aol.com

Philippe Mammillot

The Va Medical Center and Georgetown University and the George Washington University Washington D.C. USA

Robert Redman

The Va Medical Center and Georgetown University and the George Washington University Washington D.C. USA

Aldo Notargiacomo

The Va Medical Center and Georgetown University and the George Washington University Washington D.C. USA

Puneet Narayan

The Va Medical Center and Georgetown University and the George Washington University Washington D.C. USA

Raj Lakshman

The Va Medical Center and Georgetown University and the George Washington University Washington D.C. USA

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 AT 1-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.

Key Words: telmisartan • lisinopril • antihypertensive • hypertension • diabetes • renoprotection • angiotensin II receptor antagonist

Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1 suppl, S77-S80 (2001)
DOI: 10.1177/14703203010020011301
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