ET(A)-RECEPTOR ANTAGONIST PREVENTS AND REVERSES CHRONIC HYPOXIA-INDUCED PULMONARY-HYPERTENSION IN RAT
ET(A)-RECEPTOR ANTAGONIST PREVENTS AND REVERSES CHRONIC HYPOXIA-INDUCED PULMONARY-HYPERTENSION IN RAT
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DOI：
10.1152/ajplung.1995.269.5.l690
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发表时间：
1995-11-01
影响因子：
4.9
通讯作者：
OPARIL, S
中科院分区：
文献类型：
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作者：
DICARLO, VS;CHEN, SJ;OPARIL, S
选择性内皮素A（ET（A））受体拮抗剂BQ-123已被证明可预防慢性缺氧诱导的大鼠肺动脉高压。因此，在当前的研究中，我们使用BQ-123来检验以下假设：阻断ET（A）受体可以逆转以及防止平均肺动脉压、右心室与左心室加间隔比率和小动脉壁厚度百分比的增加。（50-100 μ m）的肺动脉中观察到的雄性Sprague-Dawley大鼠暴露于常压缺氧（10%O-2，2周）。输注BQ-123（0.4mg. 0.5μ l（-1）。缺氧2 wk后开始的10%O-2中持续2 wk（h（-1））可显著逆转已建立的肺动脉高压，并阻止缺氧第3和第4周时右心室肥厚的进一步发展。在暴露于缺氧之前进行的BQ-123输注完全防止了缺氧诱导的肺动脉高压、右心室肥大和肺血管重构。这些结果表明，在肺中，缺氧诱导内皮素-l的合成增加，其局部作用于ET（A）受体，引起肺动脉高压、右心肥大和肺血管重构，而ET（A）受体阻断剂可以预防和逆转这些过程。
The selective endothelin-A (ET(A))-receptor antagonist BQ-123 has been shown to prevent chronic hypoxia-induced pulmonary hypertension in the rat. Therefore in the current study we utilized BQ-123 to test the hypothesis that blockade of the ET(A) receptor can reverse as well as prevent the increase in mean pulmonary artery pressure, right ventricle-to-left ventricle plus septum ratio, and percent wall thickness in small. (50-100 mu m) pulmonary arteries observed in male Sprague-Dawley rats exposed to normobaric hypoxia (10% O-2, 2 wk). Infusion of BQ-123 (0.4 mg . 0.5 mu l(-1) . h(-1) for 2 wk in 10% O-2) begun after 2 wk of hypoxia significantly reversed the established pulmonary hypertension and prevented further progression of right ventricular hypertrophy during the third and fourth week of hypoxia. BQ-123 infusion instituted before exposure to hypoxia completely prevented the hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular remodeling. These findings suggest that, in the lung, hypoxia induced an increase synthesis of endothelin-l, which acts locally on ET(A) receptors to cause pulmonary hypertension, right heart hypertrophy, and pulmonary vascular remodeling, while ET(A)-receptor blockade can both prevent and reverse these processes.