Key result
Chronic high-altitude hypoxia significantly lowers blood pressure in spontaneously hypertensive rats.
Why the study?
The study was designed to assess the effects of chronic high-altitude hypoxia on blood pressure regulation, cardiovascular remodelling, hemodynamic alterations, and renin-angiotensin system modulation in hypertensive and normotensive rats.
Does long-term high-altitude hypoxic exposure reduce blood pressure and modulate the renin-angiotensin system in spontaneously hypertensive rats?
Does long-term high-altitude hypoxic exposure reduce blood pressure and modulate the renin-angiotensin system in spontaneously hypertensive rats?
p-value: p=<0.05
Long-term high-altitude hypoxia paradoxically reduces blood pressure in hypertensive rats via down-regulation of the renin-angiotensin system, but at the steep physiological cost of cardiac functional decline and multi-organ damage.
Introduction: 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. Methods: : 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. Results: 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. Conclusion: 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.
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Duo et al. (2025) studied Hypertension (spontaneously hypertensive rats) (n=24). High-altitude hypoxic conditions vs. Control conditions (1,660 m altitude; PaO2 17.5 kPa) was evaluated on Blood pressure (systolic, diastolic, mean arterial pressure) (p=<0.05). Long-term high-altitude hypoxic exposure significantly reduced systolic, diastolic, and mean arterial blood pressures in spontaneously hypertensive rats compared to controls.
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