THE ANGIOTENSIN-II RECEPTOR ANTAGONIST, LOSARTAN, INHIBITS LDL LIPID-PEROXIDATION AND ATHEROSCLEROSIS IN APOLIPOPROTEIN E-DEFICIENT MICE

The potential antiatherogenic actions of the angiotensin II receptor a ntagonist, losartan were investigated in apolipoprotein (apo) E defici ent mice, an animal model with severe hypercholesterolemia and extensi ve atherosclerosis. In these animals accelerated atherosclerosis is as sociated with increased lipid peroxidation which may play a crucial ro le in the build up of the atherosclerotic lesions. Administration of l osartan (25mg/kg/d) to the apo E deficient mice for a 3-month period i ncreased the plasma renin activity 3.5-fold compared to the placebo gr oup. Losartan increased the resistance of LDL to CuSO4-induced oxidati ve modification as shown by a significant reduction in the LDL content of malondialdehyde by 55% compared to placebo, as well as by the prol ongation of the lag time required for LDL oxidation, from 60 min in th e placebo-treated mice to more than 140 min in the losartan-treated mi ce. Losartan reduced significantly the mean atherosclerotic lesion are a by 80% compared to the placebo group. We conclude that losartan inhi bits LDL lipid peroxidation in the apo E deficient mice and this effec t may have an important role in the attenuation of the accelerated ath erosclerosis. (C) 1997 Academic Press.