Chronic Intermittent Hypobaric Hypoxia Decreases High Blood Pressure by Stabilizing the Vascular Renin-Angiotensin System in Spontaneously Hypertensive Rats.
Chronic Intermittent Hypobaric Hypoxia Decreases High Blood Pressure by Stabilizing the Vascular Renin-Angiotensin System in Spontaneously Hypertensive Rats.
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DOI：
10.3389/fphys.2021.639454
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发表时间：
2021
影响因子：
4
通讯作者：
Ma H
中科院分区：
文献类型：
--
作者：
Chen H;Yu B;Guo X;Hua H;Cui F;Guan Y;Tian Y;Zhang X;Zhang Y;Ma H
已有研究证实慢性间歇性低压缺氧（CIHH）对高血压大鼠的降压作用。本研究探讨了CIHH对自发性高血压大鼠（SHR）的降压作用以及肾素-血管紧张素系统（RAS）在CIHH降压作用中的作用。将15周龄雄性SHR和WKY大鼠分为4组：未给药的SHR组（SHR- con）、给药的SHR组（SHR-CIHH）、未给药的WKY组（WKY- con）和给药的WKY组（WKY-CIHH）。SHR-CIHH和WKY-CIHH大鼠进行模拟海拔4000 m的低气压缺氧35天，每天5小时。采用生物遥测法记录动脉血压和心率，采用酶联免疫吸附法（ELISA）和免疫组化法分别测定血清和肠系膜动脉血管紧张素（Ang） II、Ang1-7、白细胞介素(IL)-6、肿瘤坏死因子-α (TNF)-α、IL-10。采用微血管张力记录技术测定肠系膜动脉的收缩和舒张情况。苏木精、伊红染色及马松染色观察血管形态及纤维化情况。Western blot检测肠系膜动脉血管紧张素转换酶（ACE）、ACE2、AT1、Mas蛋白的表达。生物遥测结果显示，CIHH降低SHR患者动脉血压3 ~ 4周（P < 0.01）。ELISA和免疫组化结果显示，CIHH降低SHR血清和肠系膜动脉Ang1-7，升高Ang1-7。cihh治疗SHR组血清及肠系膜动脉IL-6、TNF-α降低，IL-10升高（P < 0.05 ~ 0.01）。微血管张力结果显示，CIHH抑制血管收缩，使SHR肠系膜动脉Ang1-7降低（P < 0.05 ~ 0.01）。结果显示，CIHH可显著改善SHR的血管重构和纤维化。western blot结果显示，CIHH上调ACE2和Mas蛋白的表达，下调ACE和AT1蛋白的表达（P < 0.05 ~ 0.01）。CIHH降低SHR高血压可能是通过抑制RAS活性，下调ACE-Ang II-AT1轴和上调ACE2-(Ang1-7)- mas轴，导致血管重构和纤维化拮抗，减少炎症，增强血管舒张。
Previous 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. Fifteen-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. The 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). CIHH 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.
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DOI：
10.1186/s12950-015-0068-1
发表时间：
2015
期刊：
Journal of inflammation (London, England)
影响因子：
--
作者：
Shi M;Cui F;Liu AJ;Ma HJ;Cheng M;Song SX;Yuan F;Li DP;Zhang Y
通讯作者：
Zhang Y
影响因子：
20.1
作者：
MULVANY, MJ;HALPERN, W
通讯作者：
HALPERN, W
影响因子：
12.3
作者：
Park, Sang Woong;Shin, Kyung Chul;Choi, Bok Hee
通讯作者：
Choi, Bok Hee
DOI：
10.1007/978-94-024-1079-2_63
发表时间：
2017-01-01
期刊：
TAURINE 10
影响因子：
--
作者：
Liang, Weiwei;Yang, Qunhui;Hu, Jianmin
通讯作者：
Hu, Jianmin
影响因子：
5.6
作者：
Alanazi, Ahmed Z.;Clark, Michelle A.
通讯作者：
Clark, Michelle A.