The mechanism of chronic unpredictable mild stress induced high blood pressure in rats: a proteomic and targeted metabolomic analysis†

Chronic stress, a leading factor for high blood pressure (BP) and even hypertension, affects health quality seriously. However, the management is rather difficult in our rapidly developing modern society, and the underlying mechanism that caused hypertension remains incompletely understood. In this study, we established a rat model of high BP induced by chronic unpredictable mild stress (CUMS). The results showed that CUMS increased the BP and heart rate, as well as the concentrations of CORT, NA, and ACTH. Based on tandem mass tag (TMT)-labeled proteomics, 13 proteins changed in RVLM. Then, targeted metabolomics together with real-time qPCR were applied to validate the levels of the biomolecules quantitatively. The related molecules were confirmed to reveal that CUMS has a great role in the upregulation of muscle contraction, synthesis of cAMP and transport of metals, while down-regulating ralaxin signaling. This finding facilitates a better understanding of the mechanism of hypertension induced by chronic stress and could provide an insight into the prevention and treatment of hypertension.