Huang Yu-fang, Li Zhi-chao, Luan Li-li, Dong Ming-qing, Zhang Bo
Department of Pathophysiology, the Fourth Military Medical University, Xi'an 710032, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2007 Nov;23(4):473-7.
To study the effects of endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) on the mechanism of hypoxic pulmonary hypertension (HPH).
We studied 4 groups of age-controlled male rats, i.e., normal control for 2 weeks group (N2), normal control for 3 weeks group (N3), exposed to hypoxia for 2 weeks group (H2) and for 3 weeks group (H3). Chronic HPH rat models were established by chronic hypobaric hypoxia [(10.0% +/- 0.5% O2] for 2 and 3 weeks, respectively. The rats were anesthetized and fixed, and the levels of mean pulmonary artery pressure (mPAP) and carotid arterial pressure (CAP) were measured using catheters by a microcomputer via transducers. The weight ratio of right ventricle (RV) and left ventricle and septum (LV + S) [RV/ (LV+S)] were determined. The contents of ET-1 in plasma of pulmonary artery and carotid artery and in homogenates of lung and systemic arteries were determined by radioimmunoassay, and the contents of VEGF in serum of pulmonary artery and carotid artery were determined by ABC-ELISA.
HPH rat models were established successfully. Compared with control groups, the values of ET-1 were both enhanced in carotid artery and pulmonary artery plasma in model groups (P < 0.01). In the HPH groups, the level of pulmonary artery plasma ET-1 was significantly lower than that of carotid artery plasma, but just the reverse was ET-1 in control rats. The levels of ET-1 in homogenates of lungs from HPH models were significantly higher than those in homogenates of lungs from control groups (P < 0.01), and markedly higher than those in homogenates of systemic arteries from HPH rats (P < 0.01) SThe values of VEGF in serum of pulmonary artery from H3 group were significantly higher than those from control groups and H2 group (P < 0.01). In serum of carotid artery, the values of VEGF from the HPH models were higher than those from the control groups (P < 0.01).
ET-1 and VEGF play important roles in the pathogenesis of HPH. The result that ET-1 concentration around pulmonary arteries was significantly higher than that around systemic arteries may be one of the mechanisms accounting for the different reaction of them to hypoxia.
研究内皮素 -1（ET -1）和血管内皮生长因子（VEGF）在低氧性肺动脉高压（HPH）发病机制中的作用。
我们研究了4组年龄匹配的雄性大鼠，即正常对照2周组（N2）、正常对照3周组（N3）、低氧暴露2周组（H2）和低氧暴露3周组（H3）。分别通过慢性低压低氧[（10.0%±0.5% O₂]2周和3周建立慢性HPH大鼠模型。将大鼠麻醉固定后，通过导管经传感器用微型计算机测量平均肺动脉压（mPAP）和颈动脉压（CAP）。测定右心室（RV）与左心室及室间隔（LV + S）的重量比[RV /（LV + S）]。采用放射免疫法测定肺动脉和颈动脉血浆以及肺和体动脉匀浆中ET -1的含量，采用ABC - ELISA法测定肺动脉和颈动脉血清中VEGF的含量。
成功建立HPH大鼠模型。与对照组相比，模型组颈动脉和肺动脉血浆中ET -1值均升高（P < 0.01）。在HPH组中，肺动脉血浆ET -1水平显著低于颈动脉血浆，但在对照大鼠中情况相反。HPH模型肺匀浆中ET -1水平显著高于对照组肺匀浆（P < 0.01），且显著高于HPH大鼠体动脉匀浆（P < 0.01）。H3组肺动脉血清中VEGF值显著高于对照组和H2组（P < 0.01）。在颈动脉血清中，HPH模型的VEGF值高于对照组（P < 0.01）。
ET -1和VEGF在HPH发病机制中起重要作用。肺动脉周围ET -1浓度显著高于体动脉周围的结果可能是它们对低氧反应不同的机制之一。
