Several in vivo studies have demonstrated that noradrenaline infusion, at concentrations producing a similar degree of hypertension to Ang II infusion, does not cause vascular hypertrophy.30 In endothelial cell-specific BH4 deficient mice, it is likely that increased endothelial cell ROS/H2O2 production, because of eNOS uncoupling, activates and primes the underlying VSMC, which in turn promote vascular hypertrophy in response to Ang II. This evidence concerns the gene AGT and hypertensive disorder.