We postulated that vascular oxidative stress injury was an underlying mechanism of changes in the NOS-NO system because of the increased superoxide levels in HU rat cerebral arteries. As expected, NADPH oxidase accounts for the enhanced vascular superoxide production and impaired endothelium-dependent relaxation of HU rat cerebral arteries, and NADPH oxidase inhibition with apocynin reverses the vascular responses to vasoconstrictors and vasodilators. In this work, we confirmed the increased cytoplasmic superoxide production in 4-week HU rat cerebral VSMCs using DHE probe, which was a enuated by mitoTEMPO. Although oxidative stress injury in HU rat cerebral Coptisine-chloride arteries is confirmed during HU, the molecular mechanism remains to be established. Superoxide production by NADPH oxidases is implicated in the pathogenesis of Loganin cardiovascular diseases. The NADPH oxidases are critical mediators of cardiovascular physiology and pathophysiology, which includes seven catalytic subunits termed Nox1-5 and Duox1 and Duox2, regulatory subunits p22phox, p47phox, Noxo1, p67phox, Noxa1, p40phox, and the major binding partner Rac. The NADPH oxidase isoforms Nox1, 2, 4, and 5 are expressed in the vasculature and are different in the activity, responses to stimuli, and type of ROS released. Nox2 and Nox4 regulate the redox status in cerebral arteries. We have provided the first evidence that not only the expression of Nox2/Nox4 but also the total activity of NADPH oxidases were increased in 4-week HU rat cerebral arteries. These results could be er explain why NADPH oxidase inhibition with apocynin restored impaired endothelium-dependent relaxation in our 
previous work. Nox2 promotes the development of endothelial dysfunction, hypertension, and inflammation, and Nox4 protects the vasculature during stress. The Nox4 might function as an inducible Nox isoform because of close correlation between Nox4 mRNA and ROS generation. The overexpression of endothelial Nox4 exerts vasodilation, which is a ributable to increased H2O2 production and decreased NO inactivation. These data seem contrary to Lee��s that Nox4 contributed to ROS generation in both cytoplasm and mitochondria triggered by Ang II. Superoxide derived from the Nox2 isoform plays important roles in angiotensin II-mediated inward remodeling and promotes hypertrophy and causes endothelial dysfunction in cerebral arterioles, possibly involving interaction with NO. Nox2 mutation exhibits a significant increase in forearm-mediated vasodilation with increased NO bioavailability. Nox2 deficiency protects against hypercholesterolemiainduced impairment of neovascularization, which is linked to decreased ROS production. A recent study by Wenzel and co-contributors found that Nox2 in infiltrating monocytes and macrophages was also accounts for angiotensin II-induced vascular dysfunction and arterial hypertension. Taken together, these data suggest of complicated roles of NADPH oxidases in the pathogenesis of cardiovascular diseases. We have demonstrated that NADPH oxidase inhibition with apocynin restored the expression and the activity of NADPH oxidases in another work;however, the roles and regulatory mechanism of Nox2/Nox4 remain to be established.