The intervention of enalapril maleate and folic acid tablet on the expressions of the GRP78 and CHOP and vascular remodeling in the vascular smooth muscle cells of H-hypertensive rats with homocysteine

F. Lu, L.-Y. Zhao, Z.-M. Zhang, Q. Zou, X.-L. Yu, C.-Y. Wei

Department of Cardiology, Tangdu Hospital, Fourth Military University, Beidaihe Sanatorium of Beijing Military Region, Fourth Hospital of Hebei Medical University, Xian, Shaanxi, China. lianyouzhaot@21cn.com

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• Pharmacology

OBJECTIVE: GRP78 and CHOP play essential roles in endoplasmic reticulum stress (ERS) of the vascular smooth muscle cells. We aim to investigate the effect of enalapril maleate and folic acid tablet on the expressions of GRP78 and CHOP and vascular remodeling in a homocysteine (HCY)-treated hypertensive rat model.

MATERIALS AND METHODS: The hypertensive rat model was established with the technique of coarctation in the abdominal aorta, and the blood pressure of the rat was measured with the non-destructive tail-cuff method two weeks after operation. Thirty-six rats with hypertension were randomly divided into 3 groups (n=12 in each group). The control group received common diet and double distilled water, methionine group received 30 g/L methionine diet and double distilled water, while enalapril maleate and folic acid tablet group received 30 g/L methionine diet and 0.2 mg.kg-1.d-1 solution of enalapril maleate and folic acid tablet. Samples were collected at week 4 and week 8 for analysis. The plasma homocysteine was measured by homocysteine detector; MAP was detected through carotid artery incubation and aortic media thickness was determined by image analyses software. The expression of GRP78 and CHOP in the vascular smooth muscle cells were identified by immunohistochemistry and Western blot.

RESULTS: Compared with the control group, the concentration of HCY in the serum of rats in methionine group was increased significantly after 4 weeks (p < 0.01), and even more significant after 8 weeks (p < 0.01). Compared with that of methionine group, the level of HCY in enalapril maleate and folic acid tablet group rats was significantly decreased (p < 0.01). The level of MAP in methionine group was increased significantly after 8 weeks compared with that of control group (p < 0.05). However, the MAP in enalapril maleate and folic acid tablet group was decreased significantly compared with that of methionine group. Compared with control group, the media thickness of vascular smooth muscle of rats in the methionine group was increased significantly (p < 0.05) while was statistically reduced in the enalapril maleate and folic acid tablet group (p < 0.05). The expressions of GRP78 and CHOP in methionine group were significantly elevated compared to that of control in a time dependent manner (p < 0.05), which were remarkably down regulated in enalapril maleate and folic acid tablet group compared with that in methionine group.

CONCLUSIONS: The administration of enalapril maleate and folic acid tablet can maintain the normal state of cells via the alleviation of ERS and vascular damages, reduction of HCY and the thickness of arterial media as well as the improvement of vascular remodeling.

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