Mechanisms of Cardiovascular Protection Associated with Intermittent Hypobaric Hypoxia Exposure in a Rat Model: Role of Oxidative Stress.
Mechanisms of Cardiovascular Protection Associated with Intermittent Hypobaric Hypoxia Exposure in a Rat Model: Role of Oxidative Stress.
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DOI：
10.3390/ijms19020366
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发表时间：
2018-01-26
影响因子：
5.6
通讯作者：
Castillo RL
中科院分区：
文献类型：
--
作者：
Aguilar M;González-Candia A;Rodríguez J;Carrasco-Pozo C;Cañas D;García-Herrera C;Herrera EA;Castillo RL
全世界有1.4亿人(以慢性或间歇性的形式)在海拔2500米以上的地方生活和工作，3500万人生活在安第斯山脉。此外，在智利，估计有55000人在高空轮班工作，在低地工作，在高地工作。研究表明，急性暴露在高海拔地区会导致健康的低海拔人群氧化应激，这是因为自由基的形成增加，抗氧化能力降低。然而，在动物模型中，间歇性低氧(IH)可诱导预适应、类反应和心脏保护。在这里，我们的目的是在一个大鼠模型中描述4个周期的间歇性低压缺氧(IHH)对心脏和血管功能的反应。成年Wistar大鼠12只，随机分为两组，每组10只，每组10只。在低压舱中连续4个周期(1个周期=缺氧4d+常氧4d)诱导间歇性低氧，达到相当于海拔4600m(428Torr)的大气压。在第一个和第四个周期结束时，通过超声心动图确定心脏结构和功能变量。然后，通过线状肌图仪测定股动脉的体外血管功能和生物力学特性。我们进一步测定了心脏氧化应激生物标记物(4-羟基-壬烯醛，HNE；硝基酪氨酸，NT)、活性氧(ROS)来源(NADPH和线粒体)，以及抗氧化酶活性(过氧化氢酶，CAT；谷胱甘肽过氧化物酶，GPX和超氧化物歧化酶，SOD)。我们的结果显示，在第四周期结束时，左心功能的射血和缩短分数较高。此外，股血管表现出血管扩张能力的改善和僵硬的减少。与常压低氧对照组相比，IHH组大鼠心肌组织中抗氧化酶的表达和线粒体ROS的形成较高。IHH暴露决定了心脏和股动脉在结构和功能水平上的预适应效应，这与抗氧化防御机制的诱导有关。然而，心肌组织中线粒体ROS的生成增加。这些发现表明，IHH的初始状态对心血管功能和保护是有益的。
More than 140 million people live and works (in a chronic or intermittent form) above 2500 m worldwide and 35 million live in the Andean Mountains. Furthermore, in Chile, it is estimated that 55,000 persons work in high altitude shifts, where stays at lowlands and interspersed with working stays at highlands. Acute exposure to high altitude has been shown to induce oxidative stress in healthy human lowlanders, due to an increase in free radical formation and a decrease in antioxidant capacity. However, in animal models, intermittent hypoxia (IH) induce preconditioning, like responses and cardioprotection. Here, we aimed to describe in a rat model the responses on cardiac and vascular function to 4 cycles of intermittent hypobaric hypoxia (IHH). Twelve adult Wistar rats were randomly divided into two equal groups, a four-cycle of IHH, and a normobaric hypoxic control. Intermittent hypoxia was induced in a hypobaric chamber in four continuous cycles (1 cycle = 4 days hypoxia + 4 days normoxia), reaching a barometric pressure equivalent to 4600 m of altitude (428 Torr). At the end of the first and fourth cycle, cardiac structural, and functional variables were determined by echocardiography. Thereafter, ex vivo vascular function and biomechanical properties were determined in femoral arteries by wire myography. We further measured cardiac oxidative stress biomarkers (4-Hydroxy-nonenal, HNE; nytrotirosine, NT), reactive oxygen species (ROS) sources (NADPH and mitochondrial), and antioxidant enzymes activity (catalase, CAT; glutathione peroxidase, GPx, and superoxide dismutase, SOD). Our results show a higher ejection and shortening fraction of the left ventricle function by the end of the 4th cycle. Further, femoral vessels showed an improvement of vasodilator capacity and diminished stiffening. Cardiac tissue presented a higher expression of antioxidant enzymes and mitochondrial ROS formation in IHH, as compared with normobaric hypoxic controls. IHH exposure determines a preconditioning effect on the heart and femoral artery, both at structural and functional levels, associated with the induction of antioxidant defence mechanisms. However, mitochondrial ROS generation was increased in cardiac tissue. These findings suggest that initial states of IHH are beneficial for cardiovascular function and protection.
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影响因子：
5.4
作者：
Herrera EA;Farías JG;González-Candia A;Short SE;Carrasco-Pozo C;Castillo RL
通讯作者：
Castillo RL
影响因子：
8.2
作者：
Guo, Hui-cai;Zhang, Zhe;Wang, Yong-li
通讯作者：
Wang, Yong-li
影响因子：
2.3
作者：
Dosek, Agoston;Ohno, Hideko;Radak, Zsolt
通讯作者：
Radak, Zsolt
影响因子：
2.3
作者：
Harper, Ronald M.;Kumar, Rajesh;Ogren, Jennifer A.;Macey, Paul M.
通讯作者：
Macey, Paul M.
影响因子：
2.1
作者：
Anderson, John D.;Honigman, Benjamin
通讯作者：
Honigman, Benjamin