Fig. 11.

The proposed effects of ROS generation in the vascular endothelium. Superoxide is produced by endothelial nitric oxide synthase (eNOS) uncoupling and NADPH oxidases. Superoxide quickly reacts with nitric oxide (NO) to produce ONOO⁻. Endogenous SOD scavenges superoxide, which produces the vasodilator H₂O₂. In the presence of catalytic transition metals (i.e., Fe²⁺), H₂O₂ can produce the potent vasoconstrictor OH⁻. In the presence of catalase or Gpx-1, H₂O₂ is converted to H₂O and O₂. ONOO⁻ is a potential NO donor; however, this capacity is inhibited when ONOO⁻ is decomposed with FeTPPS or when tempol scavenges O₂⁻, especially in old animals. H₂O₂ acts as an endothelial-derived hyperpolarization factor (EDHF); however, this capacity is blunted with tempol, which increases O₂⁻-derived H₂O₂ increasing OH⁻ production, or with tempol plus catalase, which drives the formation of H₂O and O₂ formation.