title: Prevention of atherosclerosis by specific AT1-receptor blockade with candesartan cilexetil.
abstract: 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.
authors.affiliation: The Va Medical Center and Georgetown University and the George Washington University Washington D.C. USA, papavip@ aol.com.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Papademetriou
authors.affiliation: The Va Medical Center and Georgetown University and the George Washington University Washington D.C. USA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Mammillot
authors.affiliation: The Va Medical Center and Georgetown University and the George Washington University Washington D.C. USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Redman
authors.affiliation: The Va Medical Center and Georgetown University and the George Washington University Washington D.C. USA.
authors.forename: Aldo
authors.initials: A
authors.lastname: Notargiacomo
authors.affiliation: The Va Medical Center and Georgetown University and the George Washington University Washington D.C. USA.
authors.forename: Puneet
authors.initials: P
authors.lastname: Narayan
authors.affiliation: The Va Medical Center and Georgetown University and the George Washington University Washington D.C. USA.
authors.forename: Raj
authors.initials: R
authors.lastname: Lakshman
keywords: angiotensin II receptor antagonist; antihypertensive; diabetes; hypertension; lisinopril; renoprotection; telmisartan