Figure 1.
A: increased reactive oxygen species (ROS) contribute to reductions in nitric oxide (NO) bioavailability and associated reductions in endothelium-dependent dilation. The inducible transcription factor nuclear factor-κB (NF-κB) is a critical upstream regulator of both the inflammatory and redox state of vascular endothelial cells and its activation has been directly linked to oxidative stress-mediated reductions in NO bioavailability and subsequent arterial dysfunction. Here, we evaluated the effect of short-term administration of the anti-inflammatory nonacetylated salicylate (e.g., salsalate, an inhibitor of NF-κB activation) on the mechanisms contributing to blunted endothelium-dependent dilation in young adults with major depressive disorder (MDD). We hypothesized that salsalate administration would improve NO-dependent dilation in young adults with MDD, in part, by suppressing ROS. Please note the interconnected linkage between oxidative stress and inflammation, and the directionality of signaling pathway activation, is complex and discussed in depth in several excellent review articles (33, 34). B: experimental protocol for the assessment of microvascular endothelial function; this testing occurred before (day 0) and immediately after (day 5) short-term salsalate administration. Each dotted arrow reflects the perfusion of selected pharmacological agents via intradermal microdialysis. See text for additional detail. ACh, acetylcholine; l-NAME, NG-nitro-l-arginine methyl ester; SNP, sodium nitroprusside.