PTGS2 and endothelial dysfunction: Clinical trials and experimental studies have demonstrated that COX-2 inhibitors can produce adjuvant antidepressant therapeutic effects against selective 5-HT reuptake inhibitors (59), while chronic selective 5-HT reuptake inhibition improves the endothelium-dependent hyperpolarization-like pathway of the small arteries in the fraction of endothelial function and COX-2 levels, modulating endothelial dysfunction and oxidative status in a chronic mild stress model in depressed rats (60).