In a study on mice, Wassmann et al. (2002) used a selective estrogen receptor modulator, raloxifene, which increased the activity of endothelial NO synthase and the dependence of ER in reducing the release of ROS from blood vessel cells to improve endothelial dysfunction caused by high blood pressure; these vascular effects led to a significant reduction in blood pressure and vascular injury in male spontaneously hypertensive rats. Here, ESR1 is linked to hypertensive disorder.