Systemically, ROS (produced by neutrophils (Lee et al., 2003a,b) or directly in vascular endothelial cells) can further exacerbate endothelial dysfunction, leading to endothelin-1 production and reduced NO bioavailability, which ultimately lead to hypertension via increased total peripheral resistance (TPR; George and Granger, 2011). The gene discussed is EDN1; the disease is hypertensive disorder.