NOS3 and endothelial dysfunction: ,8,9 Recently, we demonstrated in in vivo and in vitro studies that vatalanib, a VEGFi, increased the generation of reactive oxygen species (ROS) in vascular cells and decreased activation of endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO) resulting in endothelial dysfunction and vascular hypercontractility in VEGFi-treated mice.10