There is an increase in the generation of reactive oxygen species and nitric oxide in the cerebral microcirculation in Alzheimer's disease. The factors that cause this increase in oxidative stress have not been identified. Increasing evidence suggests that there are common mechanisms in atherosclerosis and Alzheimer's disease. The objective of this study was to determine the effects of oxidized low density lipoproteins (LDLs) on brain endothelial cells. Cultured rat brain endothelial cells were treated with either native LDL (10mug/ml) or LDL oxidized in vitro using 4-hydroxy-2-nonenal (HNE-LDL) (10mug/ml), for 24h. The results showed that HNE-LDL significantly increased production of nitric oxide (p < 0.01), decreased membrane fluidity (p < 0.05), and increased reactive oxygen species generation (p < 0.01). These data demonstrate that oxidized LDLs affect nitric oxide and radical generation in brain endothelial cells and could contribute to cerebrovascular dysfunction in Alzheimer's disease. (C) 2003 Elsevier Inc. All rights reserved.