Abstract: AIM The aim of the study was to investigate the relationship between changes in inositol requiring enzyme 1α(IRE1α)and c-Jun N-terminal kinases (p-JNK) expression and reversal vascular remodeling (VR) in hypertensive rats with hyperhomocystinemia (HHcy) in vascular smooth muscle cells (VSMCs) Additionally, the effects of enalopril folic acid tablet intervention were evaluated.METHODS Sixty male SD rats underwent abdominal aortic constriction (PAAC). Two weeks after operation, 36 rats with systolic blood pressure (SBP)>140 mmHg were randomly divided into three groups: control, model, and enalapril folic acid tablet (n=12). The control group and the model group was given normal diet and 25 g/L methionine diet, respectively. The enalapril folic acid tablets group was given 25 g/L methionine diet and enalapril folic acid tablets10 mg/(kg·d).Caudal arterial SBP and blood serum homocysteine (Hcy) were measured at 2, 6, and 10 weeks after operation.Ten weeks after operation, morphological changes of VSMCs were observed by hematoxylin-eosin staining (HE), the thoracic aorta intima-media thickness (IMT) was measured by Image Pro Plus 6.0 image analyses and the expressions level of rat thoracic aorta IRE1α and p-JNK protein were detected by immunohistochemistry and Western blot.RESULTS Ten weeks after operation,the caudal artery SBP, blood serum Hcy, IMT, and expressions of IRE1α and p-JNK protein in model group were higher than those in control group (P<0.05) and the caudal artery SBP,blood serum Hcy, IMT, and expressions of IRE1α and p-JNK protein in enalapril folic acid tablets group were significantly lower than those in model group (P<0.05).CONCLUSION VSMCs IRE1α and p-JNK expressions in hypertensive rats with HHcy are activated and p-JNK expression is more dominant. Enalapril folic acid tablets had double the effect in reducing blood pressure and blood serum Hcy, mitigating VSMCs ERS, recovering endoplasmic reticulum steady-state and reversing vascular remodeling.