Objective: Oxidized low-density-lipoprotein (oxLDL) and angiotensin II (Ang II) can increase formation of reactive oxygen species in endothelial cells. However, the potential cross-talk between both risk factors, the impact of Ang II receptor 1 (AT1) receptor blockade on lipoprotein-induced oxidative stress and endothelial function and of AT1a/AT1b double knockout on oxidative stress is currently not well understood. Methods and Results: We studied the impact of native and oxidized LDL (nLDL, oxLDL) on Ang II receptor expression and formation of reactive oxygen species in primary cultures of human umbilical arterial endothelial cells (HUAEC). Native and oxLDL induced AT1 and AT2 receptor mRNA and protein expression for up to 24 h. Both lipoproteins increased intracellular AT1 receptor immunofluorescence in HUAEC. Native LDL and oxLDL activated MEK/ERK and p38 MAPK pathways in HUAEC. OxLDL induced oxLDL receptor LOX-1 expression in HUAEC. Induction of both Ang II receptors by oxLDL was reduced by AT1 receptor antagonist candesartan. OxLDL induced superoxide anion formation in HUAEC. AT1 receptor blockade prevented lipoprotein-induced oxidative stress in HUAEC like SOD. Furthermore, AT1 blockade prevented impaired endothelial function. In aortic rings of wild-type mice, oxLDL-induced vascular superoxide anion formation was reduced by AT1 blockade. Finally, deletion of AT1 receptor subtypes 1a and 1b in AT1a/AT1b double knockout mice resulted in the aorta in significant downregulation of protein expression of LOX-1, Nox subunits Nox2, p47phox and p22phox, compared with wild-type mice. Conclusion: Augmented vascular oxidative stress and endothelial dysfunction in response to lipoproteins involves induction of the AT1 receptor. Double knockout of AT1 receptors reduce LOX-1 and NAD(P)H oxidase expression. Our data suggest a cross-talk between oxidized LDL, angiotensin II and oxidative stress after AT1 blockade and in AT1a/AT1b double knockout mice.