Duo Delong, Zhu Junbo, Wang Mengyue, Wang Xuejun, Qu Ning, Li Xiangyang
Research Center for High-Altitude Medicine, Qinghai University Medical College, Xining, China.
Qinghai Red Cross Hospital, Xining, China.
Front Physiol. 2025 Apr 15;16:1565147. doi: 10.3389/fphys.2025.1565147. eCollection 2025.
This study assesses the effects of chronic high-altitude hypoxia on blood pressure regulation in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, focusing on cardiovascular remodelling, hemodynamic alterations, and renin-angiotensin system (RAS) modulation.
Eight-week-old male SHR and WKY rats were divided into four groups: the SHR high-altitude hypoxia group (SHR-H), WKY high-altitude hypoxia group (WKY-H), SHR control group (SHR-C), and WKY control group (WKY-C). The hypoxia groups were exposed to 4,300 m (PaO: 12.5 kPa) for 10 weeks. Blood pressure was measured via non-invasive tail-cuff method, cardiac function via echocardiography, and right heart pressures via catheterization. Histopathological analysis included haematoxylin and eosin and Masson/Weigert staining for organ damage and vascular remodelling, whereas RAS components were assessed using immunohistochemistry.
The results showed that chronic hypoxia significantly reduced systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHR-H rats, but not in WKY-H rats. SHR-H rats showed a reduced ejection fraction, fractional shortening, systolic left ventricular anterior wall thickness, and diastolic left ventricular anterior wall thickness, increased left ventricular diastolic diameter, and left ventricular systolic diameter, whereas WKY-H showed only ejection fraction and fractional shortening decline. Both groups developed elevated mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricular end-diastolic pressure. SHR-H rats displayed aortic medial thinning, elastic fibre degradation, increased blood viscosity, and multi-organ damage (myocardial necrosis, pulmonary fibrosis), whereas WKY-H rats showed medial thinning and erythrocyte hyperplasia without fibrosis. Immunohistochemistry revealed suppression of the angiotensin-converting enzyme (ACE)-angiotensin II (Ang II)-angiotensin II type I (AT1) axis in SHR-H, whereas WKY-H exhibited reduced Ang I/II without ACE2 and Mas receptor (MasR) changes.
Long-term hypoxic exposure at high-altitude reduces blood pressure in SHR rats, which may be attributed to a combination of cardiac functional compensation failure, vascular remodelling, and simultaneous inhibition of the ACE-Ang II-AT1R and ACE2-Ang1-7-MasR axes.
本研究评估慢性高原低氧对自发性高血压大鼠（SHR）和正常血压的Wistar-Kyoto（WKY）大鼠血压调节的影响，重点关注心血管重塑、血流动力学改变和肾素-血管紧张素系统（RAS）调节。
将8周龄雄性SHR和WKY大鼠分为四组：SHR高原低氧组（SHR-H）、WKY高原低氧组（WKY-H）、SHR对照组（SHR-C）和WKY对照组（WKY-C）。低氧组暴露于4300米（动脉血氧分压：12.5千帕）环境10周。通过无创尾套法测量血压，通过超声心动图评估心功能，通过导管插入术测量右心压力。组织病理学分析包括苏木精和伊红染色以及用于评估器官损伤和血管重塑的Masson/Weigert染色，而使用免疫组织化学评估RAS成分。
结果显示，慢性低氧显著降低了SHR-H大鼠的收缩压、舒张压和平均动脉压，但对WKY-H大鼠无此影响。SHR-H大鼠射血分数、缩短分数、左心室前壁收缩期厚度和左心室前壁舒张期厚度降低，左心室舒张末期直径和左心室收缩末期直径增加，而WKY-H大鼠仅射血分数和缩短分数下降。两组的平均肺动脉压、右心室收缩压和右心室舒张末期压力均升高。SHR-H大鼠出现主动脉中膜变薄、弹性纤维降解、血液粘度增加和多器官损伤（心肌坏死、肺纤维化），而WKY-H大鼠表现为中膜变薄和红细胞增生但无纤维化。免疫组织化学显示SHR-H中血管紧张素转换酶（ACE）-血管紧张素II（Ang II）-血管紧张素II 1型受体（AT1）轴受到抑制，而WKY-H中Ang I/II降低但ACE2和Mas受体（MasR）无变化。
长期高原低氧暴露可降低SHR大鼠血压，这可能归因于心功能代偿衰竭、血管重塑以及ACE-Ang II-AT1R和ACE2-Ang1-7-MasR轴同时受到抑制。
