1. Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats
- Author
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Qian Jiang, Qifeng Yang, Chenting Zhang, Chi Hou, Wei Hong, Min Du, Xiaoqian Shan, Xuanyi Li, Dansha Zhou, Dongmei Wen, Yuanhui Xiong, Kai Yang, Ziying Lin, Jingjing Song, Zhanjie Mo, Huazhuo Feng, Yue Xing, Xin Fu, Chunli Liu, Fang Peng, Liling Wu, Bing Li, Wenju Lu, Jason X.-J. Yuan, Jian Wang, and Yuqin Chen more...
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Chronic kidney disease ,Pulmonary hypertension ,Renin–angiotensin–aldosterone system ,Angiotensin converting enzyme 2 ,Metabolomics ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Chronic kidney disease (CKD) is a significant risk factor for pulmonary hypertension (PH), a complication that adversely affects patient prognosis. However, the mechanisms underlying this association remain poorly understood. A major obstacle to progress in this field is the lack of a reliable animal model replicating CKD-PH. Methods This study aimed to establish a stable rat model of CKD-PH. We employed a combined approach, inducing CKD through a 5/6 nephrectomy and concurrently exposing the rats to a high-salt diet. The model's hemodynamics were evaluated dynamically, alongside a comprehensive assessment of pathological changes in multiple organs. Lung tissues and serum samples were collected from the CKD-PH rats to analyze the expression of angiotensin-converting enzyme 2 (ACE2), evaluate the activity of key vascular components within the renin–angiotensin–aldosterone system (RAAS), and characterize alterations in the serum metabolic profile. Results At 14 weeks post-surgery, the CKD-PH rats displayed significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension. Additionally, right ventricular hypertrophy was observed. Notably, no evidence of pulmonary vascular remodeling was found. Further analysis revealed RAAS dysregulation and downregulated ACE2 expression within the pulmonary vascular endothelium of CKD-PH rats. Moreover, the serum metabolic profile of these animals differed markedly from the sham surgery group. Conclusions Our findings suggest that the development of pulmonary arterial hypertension in CKD-PH rats is likely a consequence of a combined effect: RAAS dysregulation, decreased ACE2 expression in pulmonary vascular endothelial cells, and metabolic disturbances. Graphical Abstract more...
- Published
- 2024
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