Psychological stress-induced cerebrovascular dysfunction: the role of metabolic syndrome and exercise

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Chronic unresolvable stress leads to the development of depression and cardiovascular disease (CVD). There is a high prevalence of depression with the metabolic syndrome (MetS), however, to what extent the MetS concurrent with psychological stress affects cerebrovascular function is unknown. We investigated the differential effect of MetS on cerebrovascular structure/function in rats (16–17-wk-old) following 8 wk of unpredictable chronic mild stress (UCMS), and whether exercise training could limit any cerebrovascular dysfunction. In healthy lean rats (LZR), UCMS decreased (28%, p<0.05) ex-vivo middle cerebral artery (MCA) endothelium-dependent dilation (EDD), however, changes in MCA remodeling and stiffness were not evident but cerebral microvessel density decreased (MVD; 30%, p<0.05). The presence of UCMS and MetS (OZR; obese Zucker rats) decreased MCA EDD (35%, p<0.05), and dilation to sodium nitroprusside (20%, p<0.05), while MCA stiffness increased, and cerebral MVD decreased (31%, p<0.05), which were linked to a reduced nitric oxide and increased oxidative levels. Aerobic exercise prevented UCMS impairments in MCA function and MVD in LZR, and partly restored MCA function, stiffness and MVD in OZR. Our data suggests that the benefits of exercise with UCMS was due to a reduction in oxidative stress, and increased production of nitric oxide in the cerebral vessels. In conclusion, UCMS significantly impaired MCA structure and function, but the effects of UCMS were more substantial in OZR vs. LZR. Importantly, aerobic exercise when combined with UCMS prevented the MCA dysfunction through subtle shifts in nitric oxide and oxidative stress in the cerebral microvasculature.