Figure 6.

Summary of redox regulatory pathways of vascular tone. Endothelial nitric oxide synthase (eNOS) and soluble guanylyl cyclase (sGC) are inactivated by a number of redox switches. Reactive oxygen and nitrogen species (ROS/RNS) also activate the 26S proteasome via 3-nitrotyrosine (3NT) modification leading to degradation of the tetrahydrobiopterin (BH₄) synthase GTP-cyclohydrolase (GCH-1) and the BH₂ to BH₄ recycling enzyme dihydrofolate reductase (DHFR). BH₄ is an essential cofactor of eNOS and also prevents oxidative inactivation of the sGC. NO is inactivated by superoxide and eNOS-derived NO prevents proteasomal DHFR degradation upon tyrosine nitration of the 26S proteasome. From Münzel and Daiber, Arterioscler. Thromb. Vasc. Biol. 2015 [135]. With permission of Wolters Kluwer Health, Inc. (Philadelphia, PA, USA). Copyright © 2015, Wolters Kluwer Health (Philadelphia, PA, USA).