Obesity Combined with Chronic Restraint Stress-Induced Hypertension in Mice Is Associated with the Damage of Noradrenergic Neurons in Nucleus Tractus Solitarii

WANG Sen-jia, ZHENG Xiang, BI Wen-jie, ZHOU Xue

Abstract

To investigate whether obesity combined with chronic restraint stress (CRS) can increase blood pressure in mice and its relationship with the damage of the intermediate part of the nucleus tractus solitarius (iNTS).  Methods  The CRS mouse model was constructed, and 51 mice were assigned to four groups, low-fat diet non-restraint group (LF group), low-fat diet restraint group (LS group), high-fat diet non-restraint group (HF group), and high-fat diet restraint group (HS group). Interventions were carried out in four cycles (over the course of 40 consecutive days), with each cycle consisting of 7 days of restraint and 3 days of free movement. The body weight and the arterial systolic blood pressure of the mice were measured on the day 9 of every cycle. The mice were sacrificed on day 40 and the brain tissues of the mice were collected afterwards in order to perform immunohistochemical staining and Western blot to examine the expression of glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH). The protein expression of vascular endothelial growth factor A (VEGFA) was examined with Western blot on epididymal fat pad to assess the vascular density of lipid tissue.  Results   On day 40, the arterial systolic pressure of mice in HS group was significantly higher than that of mice in the three other groups. Body mass of high-fat diet group (HF group and HS group) increased significantly. Mice in the four groups did not present significant difference in VEGFA protein expression. INTS astrocytes were activated in the brain of mice in the restraint groups (LS group and HS group), and iNTS TH expression was decreased in HS group. Mice in HF group and LS group did not show abnormal changes in their blood pressure. Blood pressure of mice in the HS group generally rose, and hypertension (arterial systolic blood pressure ≥140 mmHg, 1 mmHg=0.133 kPa) was observed in 37.5% of the mice in this group.  Conclusion   Obesity combined with CRS may cause an increase in arterial blood pressure in mice, the mechanism of which may be related to the damage of noradrenergic neurons in the nucleus tractus solitarius.

 

Keywords: Chronic restraint stress, High-fat diet, Noradrenergic, Neuron, Nucleus tractus solitarius

 

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