Lai Y L, Wu H D, Chen C F
Department of Physiology, College of Medicine, National Taiwan University, Taipei.
J Cardiovasc Pharmacol. 1998 Nov;32(5):714-20. doi: 10.1097/00005344-199811000-00006.
Because chronic hypoxia increases the production of oxygen radicals, we hypothesized that antioxidants attenuate chronic hypoxic pulmonary hypertension. In part 1, we examined the temporal progress in chronic hypoxic pulmonary hypertension in 46 Wistar rats exposed to hypoxia from 0-3 weeks. In part 2, we tested whether antioxidants attenuated chronic hypoxic pulmonary hypertension in 82 rats divided into 10 groups: control, fullerenol-1, U-83836E, dimethylthiourea-1, dimethylthiourea-2, hypoxia, hypoxia + fullerenol-1, hypoxia + U83836E, hypoxia + dimethylthiourea-1, and hypoxia + dimethylthiourea-2. Control animals breathed room air and were injected intraperitoneally with saline for 2 weeks. Fullerenol-1, U-83836E, and dimethylthiourea are antioxidants and were administered intraperitoneally for 2 weeks, except that dimethylthiourea was given either on days 3, 5, and 7 (dimethylthiourea-1), or on days 8, 10, and 12 (dimethylthiourea-2). Hypoxic animals were placed into a hypobaric chamber with a barometric pressure of 380 Torr for 2 weeks. Hypoxia + antioxidant groups were administered antioxidants during hypoxic exposure. We observed a gradual increase in pulmonary artery pressure, the weight ratio of right ventricle to left ventricle plus septum, and hematocrit during the 3 weeks of chronic hypoxia. These hypoxia-induced alterations were significantly attenuated by U-83836E and dimethylthiourea, but not by fullerenol-1. Neither the temporal alterations nor the antioxidant effects can be explained by the change in either tracheal neutral endopeptidase activity or the lung or plasma substance P level, perhaps because of the time lag in sampling. These results indicate that oxygen radicals play an important role in the development of chronic hypoxic pulmonary hypertension.
由于慢性缺氧会增加氧自由基的产生，我们推测抗氧化剂可减轻慢性缺氧性肺动脉高压。在第一部分中，我们研究了46只暴露于缺氧环境0至3周的Wistar大鼠慢性缺氧性肺动脉高压的时间进程。在第二部分中，我们在82只大鼠中测试了抗氧化剂是否能减轻慢性缺氧性肺动脉高压，这些大鼠被分为10组：对照组、富勒醇-1组、U-83836E组、二甲基硫脲-1组、二甲基硫脲-2组、缺氧组、缺氧 + 富勒醇-1组、缺氧 + U83836E组、缺氧 + 二甲基硫脲-1组和缺氧 + 二甲基硫脲-2组。对照动物呼吸室内空气，并腹腔注射生理盐水2周。富勒醇-1、U-83836E和二甲基硫脲是抗氧化剂，腹腔注射2周，除了二甲基硫脲在第3、5和7天给药（二甲基硫脲-1），或在第8、10和12天给药（二甲基硫脲-2）。缺氧动物被置于气压为380 Torr的低压舱中2周。缺氧 + 抗氧化剂组在缺氧暴露期间给予抗氧化剂。我们观察到在慢性缺氧的3周内，肺动脉压、右心室与左心室加室间隔的重量比以及血细胞比容逐渐增加。这些缺氧诱导的改变被U-83836E和二甲基硫脲显著减轻，但未被富勒醇-1减轻。气管中性内肽酶活性、肺或血浆P物质水平的变化均无法解释时间变化或抗氧化剂的作用，可能是由于采样存在时间滞后。这些结果表明氧自由基在慢性缺氧性肺动脉高压的发展中起重要作用。
