Nitric oxide branch of arginine metabolism in depression: effect of venlafaxine.

Objectives Major Depressive Disorder is an established independent risk factor for cardiovascular disease, but the precise pathophysiological mechanism remains obscure. The nitric oxide branch of arginine metabolism has been linked to vascular homeostasis. Methods Five plasma biomarkers of the nitric oxide branch of arginine metabolism were quantified in depressed patients (n = 22) and healthy controls (n = 17): total nitrite, nitrotyrosine, asymmetric dimethylarginine, agmatine, and myeloperoxidase. Thirteen of the depressed patients were restudied after 4-8 weeks of mood normalization with venlafaxine, a mixed serotonin/norepinephrine reuptake blocker. Results None of the biomarkers were altered in depressed patients compared to controls. However, treatment reduced agmatine and myeloperoxidase levels (p=0.02 each). A clear but nonsignificant rise in total nitrite and nitrotyrosine was also observed at week-4. Conclusions Despite no changes at pre-treatment, the reductions in agmatine and myeloperoxidase may result from serotonin and/or noradrenaline changes occurring with venlafaxine antidepressant therapy.