Major depression is known to be associated with cardiovascular abnormalities and oxidative stress has been suggested to play a role. We tested the hypothesis that antidepressant treatment reduces oxidative stress, and endothelial dysfunctions in the chronic mild stress (CMS) model of depression in rats. Rats with >30% reduction in sucrose intake after 4 weeks of CMS were defined in the study as CMS-susceptible and compared to unstressed controls. Sixteen CMS-susceptible and 8 unstressed rats were treated during weeks 5 to 8 of the CMS protocol with escitalopram. Escitalopram-treated rats with >20% recovery in the sucrose consumption during the last 2 weeks of treatment were defined as escitalopram responders. Rats which did not reach these criteria were defined as escitalopram non-responders. In the open field test escitalopram responders demonstrated anxiolytic effect of treatment. In mesenteric small arteries escitalopram affected neither NO nor COX-1 mediated vasodilation. Escitalopram potentiated endothel