Interestingly, the causative role of iNOS-mediated NO synthesis in hypoxia/reoxygenation injury is well established (Toomey et al, 2001) and NO appeared to affect the function of different proteins including NF- κB and HIF-1 by their nitrosylation (Palmer et al, 2000; Marshall and Stamler, 2001).
In addition, the results of one study suggested that the impaired vascular reactivity in migraineurs is entirely attributable to a reduced response of vascular smooth muscle cells to NO while the endothelial response to NO appeared intact [34].
Furthermore the presence of NO appeared to reduce the availability of superoxide in mitochondria in muscle fibers from both adult and old mice, but no age-related effect was seen.
The negative effect on TNFα and other macrophage derived pro-inflammatory mediators (IL-12, IFNγ and NO) appeared to be mediated through the constitutively expressed VPAC1, although the inducible expressed VPAC2 could also participate (Delgado et al., 2000).
