Chronic Intermittent Hypobaric Hypoxia Decreases High Blood Pressure by Stabilizing the Vascular Renin-Angiotensin System in Spontaneously Hypertensive Rats
Background and AimsPrevious studies have demonstrated the anti-hypertensive effect of chronic intermittent hypobaric hypoxia (CIHH) in hypertensive rats. The present study investigated the anti-hypertensive effect of CIHH in spontaneously hypertensive rats (SHR) and the role of the renin-angiotensin...
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Frontiers Media S.A.
2021-03-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.639454/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hua Chen Hua Chen Bin Yu Bin Yu Xinqi Guo Hong Hua Fang Cui Yue Guan Yanming Tian Xiangjian Zhang Yi Zhang Yi Zhang Huijie Ma Huijie Ma |
spellingShingle |
Hua Chen Hua Chen Bin Yu Bin Yu Xinqi Guo Hong Hua Fang Cui Yue Guan Yanming Tian Xiangjian Zhang Yi Zhang Yi Zhang Huijie Ma Huijie Ma Chronic Intermittent Hypobaric Hypoxia Decreases High Blood Pressure by Stabilizing the Vascular Renin-Angiotensin System in Spontaneously Hypertensive Rats Frontiers in Physiology chronic intermittent hypobaric hypoxia anti-hypertension endothelial-dependent relaxation renin-angiotensin system Ang II Ang1-7 |
author_facet |
Hua Chen Hua Chen Bin Yu Bin Yu Xinqi Guo Hong Hua Fang Cui Yue Guan Yanming Tian Xiangjian Zhang Yi Zhang Yi Zhang Huijie Ma Huijie Ma |
author_sort |
Hua Chen |
title |
Chronic Intermittent Hypobaric Hypoxia Decreases High Blood Pressure by Stabilizing the Vascular Renin-Angiotensin System in Spontaneously Hypertensive Rats |
title_short |
Chronic Intermittent Hypobaric Hypoxia Decreases High Blood Pressure by Stabilizing the Vascular Renin-Angiotensin System in Spontaneously Hypertensive Rats |
title_full |
Chronic Intermittent Hypobaric Hypoxia Decreases High Blood Pressure by Stabilizing the Vascular Renin-Angiotensin System in Spontaneously Hypertensive Rats |
title_fullStr |
Chronic Intermittent Hypobaric Hypoxia Decreases High Blood Pressure by Stabilizing the Vascular Renin-Angiotensin System in Spontaneously Hypertensive Rats |
title_full_unstemmed |
Chronic Intermittent Hypobaric Hypoxia Decreases High Blood Pressure by Stabilizing the Vascular Renin-Angiotensin System in Spontaneously Hypertensive Rats |
title_sort |
chronic intermittent hypobaric hypoxia decreases high blood pressure by stabilizing the vascular renin-angiotensin system in spontaneously hypertensive rats |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2021-03-01 |
description |
Background and AimsPrevious studies have demonstrated the anti-hypertensive effect of chronic intermittent hypobaric hypoxia (CIHH) in hypertensive rats. The present study investigated the anti-hypertensive effect of CIHH in spontaneously hypertensive rats (SHR) and the role of the renin-angiotensin system (RAS) in anti-hypertensive effect of CIHH.MethodsFifteen-week-old male SHR and WKY rats were divided into four groups: the SHR without CIHH treatment (SHR-CON), the SHR with CIHH treatment (SHR-CIHH), the WKY without CIHH treatment (WKY-CON), and the WKY with CIHH treatment (WKY-CIHH) groups. The SHR-CIHH and WKY-CIHH rats underwent 35-days of hypobaric hypoxia simulating an altitude of 4,000 m, 5 h per day. Arterial blood pressure and heart rate were recorded by biotelemetry, and angiotensin (Ang) II, Ang1–7, interleukin (IL)-6, tumor necrosis factor-alpha (TNF)-α, and IL-10 in serum and the mesenteric arteries were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The microvessel tension recording technique was used to determine the contraction and relaxation of the mesenteric arteries. Hematoxylin and eosin and Masson’s staining were used to observe vascular morphology and fibrosis. Western blot was employed to detect the expression of the angiotensin-converting enzyme (ACE), ACE2, AT1, and Mas proteins in the mesenteric artery.ResultsThe biotelemetry result showed that CIHH decreased arterial blood pressure in SHR for 3–4 weeks (P < 0.01). The ELISA and immunohistochemistry results showed that CIHH decreased Ang II, but increased Ang1–7 in serum and the mesenteric arteries of SHR. In the CIHH-treated SHR, IL-6 and TNF-α decreased in serum and the mesenteric arteries, and IL-10 increased in serum (P < 0.05–0.01). The microvessel tension results revealed that CIHH inhibited vascular contraction with decreased Ang1–7 in the mesenteric arteries of SHR (P < 0.05–0.01). The staining results revealed that CIHH significantly improved vascular remodeling and fibrosis in SHR. The western blot results demonstrated that CIHH upregulated expression of the ACE2 and Mas proteins, and downregulated expression of the ACE and AT1 proteins (P < 0.05–0.01).ConclusionCIHH decreased high blood pressure in SHR, possibly by inhibiting RAS activity, downregulating the ACE-Ang II-AT1 axis and upregulating the ACE2-(Ang1-7)-Mas axis, which resulted in antagonized vascular remodeling and fibrosis, reduced inflammation, and enhanced vascular relaxation. |
topic |
chronic intermittent hypobaric hypoxia anti-hypertension endothelial-dependent relaxation renin-angiotensin system Ang II Ang1-7 |
url |
https://www.frontiersin.org/articles/10.3389/fphys.2021.639454/full |
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doaj-077669ae9ebf47ccb16c0a90b7ece1d32021-03-24T05:05:41ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-03-011210.3389/fphys.2021.639454639454Chronic Intermittent Hypobaric Hypoxia Decreases High Blood Pressure by Stabilizing the Vascular Renin-Angiotensin System in Spontaneously Hypertensive RatsHua Chen0Hua Chen1Bin Yu2Bin Yu3Xinqi Guo4Hong Hua5Fang Cui6Yue Guan7Yanming Tian8Xiangjian Zhang9Yi Zhang10Yi Zhang11Huijie Ma12Huijie Ma13Department of Physiology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Cardiovascular Care Unit, Hebei General Hospital, Shijiazhuang, ChinaDepartment of Cardiovascular Care Unit, Hebei General Hospital, Shijiazhuang, ChinaDepartment of Emergency, Fourth Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Physiology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Physiology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Electron Microscope Experimental Centre, Hebei Medical University, Shijiazhuang, ChinaDepartment of Physiology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Physiology, Hebei Medical University, Shijiazhuang, ChinaHebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, ChinaDepartment of Physiology, Hebei Medical University, Shijiazhuang, ChinaHebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, ChinaDepartment of Physiology, Hebei Medical University, Shijiazhuang, ChinaHebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, ChinaBackground and AimsPrevious studies have demonstrated the anti-hypertensive effect of chronic intermittent hypobaric hypoxia (CIHH) in hypertensive rats. The present study investigated the anti-hypertensive effect of CIHH in spontaneously hypertensive rats (SHR) and the role of the renin-angiotensin system (RAS) in anti-hypertensive effect of CIHH.MethodsFifteen-week-old male SHR and WKY rats were divided into four groups: the SHR without CIHH treatment (SHR-CON), the SHR with CIHH treatment (SHR-CIHH), the WKY without CIHH treatment (WKY-CON), and the WKY with CIHH treatment (WKY-CIHH) groups. The SHR-CIHH and WKY-CIHH rats underwent 35-days of hypobaric hypoxia simulating an altitude of 4,000 m, 5 h per day. Arterial blood pressure and heart rate were recorded by biotelemetry, and angiotensin (Ang) II, Ang1–7, interleukin (IL)-6, tumor necrosis factor-alpha (TNF)-α, and IL-10 in serum and the mesenteric arteries were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The microvessel tension recording technique was used to determine the contraction and relaxation of the mesenteric arteries. Hematoxylin and eosin and Masson’s staining were used to observe vascular morphology and fibrosis. Western blot was employed to detect the expression of the angiotensin-converting enzyme (ACE), ACE2, AT1, and Mas proteins in the mesenteric artery.ResultsThe biotelemetry result showed that CIHH decreased arterial blood pressure in SHR for 3–4 weeks (P < 0.01). The ELISA and immunohistochemistry results showed that CIHH decreased Ang II, but increased Ang1–7 in serum and the mesenteric arteries of SHR. In the CIHH-treated SHR, IL-6 and TNF-α decreased in serum and the mesenteric arteries, and IL-10 increased in serum (P < 0.05–0.01). The microvessel tension results revealed that CIHH inhibited vascular contraction with decreased Ang1–7 in the mesenteric arteries of SHR (P < 0.05–0.01). The staining results revealed that CIHH significantly improved vascular remodeling and fibrosis in SHR. The western blot results demonstrated that CIHH upregulated expression of the ACE2 and Mas proteins, and downregulated expression of the ACE and AT1 proteins (P < 0.05–0.01).ConclusionCIHH decreased high blood pressure in SHR, possibly by inhibiting RAS activity, downregulating the ACE-Ang II-AT1 axis and upregulating the ACE2-(Ang1-7)-Mas axis, which resulted in antagonized vascular remodeling and fibrosis, reduced inflammation, and enhanced vascular relaxation.https://www.frontiersin.org/articles/10.3389/fphys.2021.639454/fullchronic intermittent hypobaric hypoxiaanti-hypertensionendothelial-dependent relaxationrenin-angiotensin systemAng IIAng1-7 |