Previous studies have demonstrated that increased level of superoxide and H2O2 enhanced Ang II–stimulated redox signaling in resistance arteries from hypertensive patients.26 The combination of increased eNOS-derived ROS and reduced eNOS-derived NO production is likely to be the major contributor toward the development of vascular dysfunction, and hence hypertension observed in Ang II–treated Gch1fl/flTie2cre mice and contrasts with eNOS knockout mice where all functions of eNOS (ie, both NO and ROS generation) are deleted. The gene discussed is AGT; the disease is hypertensive disorder.