Altered aortic vascular reactivity in the unpredictable chronic mild stress model of depression in mice: UCMS causes relaxation impairment to ACh

Major depression is an independent risk factor for the development of cardiovascular disease. This impact of depression on vascular function seems to be mediated by the endothelial dysfunction, defined as an impairment of endothelium-dependent vasorelaxation, which represents a reliable predictor of atherosclerosis and has been regularly found to be associated with depression. This study aimed at investigating aortic vascular reactivity in mice submitted to the unpredictable chronic mild stress (UCMS) procedure, a reliable model of depression. The results confirm the effectiveness of the UCMS procedure to induce neuroendocrine, physical and behavioral depression-like alterations as well as a significant decrease of acetylcholine-induced vasorelaxation without any effect on phenylephrine-induced vasoconstriction. In this study, we reveal an altered vascular reactivity in an animal model of depression, demonstrating an endothelial dysfunction reminiscent to the one found in depressed patients.

Research highlights► Endothelial dysfunction is one of the main mechanisms proposed to explain the link between depression and cardiovascular disease. ► UCMS induces physical, behavioral, motivational and neuroendocrine alterations which may parallel those observed in depressed subjects. ► The depression-like state induced by UCMS is associated with a decrease ofacetylcholine-induced aortic vasodilatation, suggesting an endothelial dysfunction. ► By using the UCMS model in mice, this study reproducesthe existing link between depression and cardiovascular alterations.