Author(s)

Congcong Zhang^1,2, Jingjing Zhang¹, Yuanling Wu¹, Yongyue Dai¹, Lei Ying¹, Wantie Wang^1*

¹Department of Pathophysiology, Wenzhou Medical University, Wenzhou, China.
²Zhejiang Pharmaceutical College, Ningbo, China.

Objective: To observe the pulmonary vascular remodeling in rats with pulmonary hypertension induced by hypoxia and hypercapnia, and to explore the role of endoplasmic reticulum stress in pulmonary hypertension. Methods: 1) 40 SD rats were randomly divided into four groups: normoxic control group (N), hypoxia hypercapnia group (HH), endoplasmic reticulum stress (ERS) inhibitor 4-phenyl butyric acid group (4-PBA), ERS pathway agonist tunicamycin group (TM). 2) The mean pulmonary arterial pressure (mPAP) and the right ventricular hypertrophy index (RV/(LV + S)) were measured in each group. 3) Identification of pulmonary artery smooth muscle cells (PASMCs) in each group by immunofluorescence α-SMA. 4) Morphological changes of lung tissue and pulmonary artery were observed by electron microscope. 5) The apoptotic index of PASMCs in each group was detected by TUNEL. 6) Reverse transcription polymerase chain reaction (RT-PCR) and Western Blot (WB) were used to detect the expression of ERS related protein and mRNA (GRP78, CHOP, JNK, Caspase-12) in each group. Results: 1) Compared with the N group, the mPAP, RV/(LV + S) and vascular wall area (WA)/total area (TA) value of HH group, 4-PBA group and TM group were increased (P < 0.01), and the vascular lumen area (LA)/TA values, PASMCs apoptosis index were significantly decreased. GRP78, CHOP, JNK, Caspase-12 expression were increased, and the differences were statistically significant. 2) Compared with the HH group, the mPAP, RV/(LV + S) and WA/TA of 4-PBA group were decreased (P < 0.01); the LA/TA value and PASMCs apoptosis index were increased (P < 0.05); and the mRNA and protein expression of CHOP, JNK, Caspase-12 and GRP78 had a significant decrease (P < 0.05). 3) Compared with the HH, the mPAP, RV/(LV + S) and WA/TA of TM group were increased (P < 0.05, P < 0.01), while LA/TA were decreased (P < 0.01); and  PASMCs apoptotic index was increased (P < 0.01). Meanwhile, the mRNA expression of Caspase-12, CHOP, JNK and GRP78 was increased to varying degrees (P < 0.05), and the protein expression of Caspase-12, CHOP and JNK was also increased significantly (P < 0.01). Conclusion: Hypoxia and hypercapnia induced pulmonary vascular remodeling may be related to the proliferation of PASMCs, and ERS related factors (JNK, Caspase12 and CHOP) are involved in the regulation of hypoxic hypercapnia.

ERS, Pulmonary Artery Hypertension, Hypoxia Hypercapnia, Rat

Zhang, C. , Zhang, J. , Wu, Y. , Dai, Y. , Ying, L. and Wang, W. (2018) Effects of Endoplasmic Reticulum Stress on Pulmonary Hypertension in Rat Induced by Chronic Hypoxia and Hypercapnia. Journal of Biosciences and Medicines, 6, 53-67. doi: 10.4236/jbm.2018.66004.