The major receptor for the uptake of oxidized low-density lipoprotein (oxLDL) in endothelial cells is the lectinlike oxLDL receptor-1 LOX-1. Here we tested whether transgenic overexpression of bovine LOX-1 in male mice (8 weeks old) fed with a high-fat Western-type diet for 10 weeks affects vascular function of the aorta and A. saphena. Similarly aged and fed C57BL/6 wildtype animals (WT) were studied for comparison. The transgene was mapped by fluorescence in situ hybridization to chromosome 3 (region 3H3-4) of the mouse genome. Phenylephrine-preconstricted vessels relaxed in response to acetylcholine (ACh). In aorta, force was reduced to 15.8±3.3% of control in LOX-1 mice and to 10.0±2.5% in WT mice. The corresponding values for A. saphena were 17.1±3.2% in LOX-1 mice and 11.7±4.1% in WT mice. ACh potency was lower in A. saphena from LOX-1 compared to WT mice (logEC50 [M] -6.5±0.1 in LOX-1 mice vs. -7.0±0.1 in WT). The endothelium derived NO fraction was unchanged in aorta (18.3±4.9% in LOX-1 mice vs. 17.0±2.6% in WT) and A. saphena (0.7±0.3% in LOX-1 mice vs. 1.8±0.4% in WT). The membrane potential in the A. saphena was -75.8±1.4 mV in LOX-1 mice and -73.3±0.5 mV in WT. We conclude that LOX-1 receptor overexpression can affect responses to vasoactive agents.