Psychological stress and endothelial dysfunction : a link between depression and vascular disease?

Abstract

Depression is increasingly recognized as a risk factor for peripheral vascular disease in patients with no history of vasculopathy; as such this study evaluated vascular function in an established mouse model of chronic depression developed for behavioral research. 20 male Balb/cj mice were exposed to 6 weeks of unpredictable chronic mild stress (UCMS) to induce depression. The UCMS protocol consisted of random exposure to stressors including damp sawdust, social stress, exposure to predator sound/smell, reversal of the day/night cycle, and cage tilt. Depressive‐like behavior was evaluated using coat status/grooming in response to sucrose spray. Isometric tension development was assessed in aortic rings in response to acetylcholine and phenylephrine. Aortic responses to phenylephrine did not differ between groups, although acetylcholine‐induced relaxation was decreased in rings from mice exposed to the UCMS protocol. Parallel experiments indicated that acetylcholine‐induced NO generation was blunted in arteries of stressed mice versus controls. However, acetylcholine‐induced release of hydrogen peroxide was increased in mice receiving UCMS versus controls. These results may suggest that depression‐like behavior in mice is associated with an impaired vascular endothelial function and altered dilator signaling. The functional implications for these responses require further investigation.