Abstract
BACKGROUND: The aim of this study was to investigate the potential mechanisms by which chronic unpredictable mild stress (CMS) might induce cardiovascular disease. METHODS: Twenty male Sprague-Dawley rats (weighing 180-250 g) were divided into the CMS group (CMS for 3 weeks) and control group (n = 10/group). Sucrose solution consumption, sucrose solution preference rate, and the open field test (horizontal and vertical movements) were used to confirm the establishment of the CMS model. Heart rate was determined in Langendorff-perfused hearts, and field action potential duration (FAPD) was measured in cardiac atrial tissue, cardiac ventricular tissue, and thoracic spinal cord segments 1-5. The expressions of serotonin (5-HT) and growth-associated protein-43 (GAP-43) in cardiac ventricular tissue were analyzed using immunohistochemistry and immunofluorescence. RESULTS: Compared with the control group, sucrose solution consumption, sucrose solution preference rate, horizontal movement, and vertical movement were significantly lower in the CMS group (P < 0.01). The CMS group exhibited significant decreases in atrial and ventricular FAPDs (P < 0.05), as well as significant increases in heart rates (P < 0.05) and T1-5 spinal cord FAPD (P < 0.01), as compared with the control group. The expressions of 5-HT and GAP-43 in cardiac ventricular tissue were significantly higher in the CMS group than in controls (P < 0.01). CONCLUSIONS: CMS causes cardiac and T1-5 spinal cord electrophysiological abnormalities as well as increased cardiac expression of 5-HT and GAP-43, indicating that CMS could potentially increase the risk of cardiovascular disease.