NORMOBARIC HYPOXIA STIMULATES ENDOTHELIN-1 GENE-EXPRESSION IN THE RAT
NORMOBARIC HYPOXIA STIMULATES ENDOTHELIN-1 GENE-EXPRESSION IN THE RAT
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DOI：
10.1152/ajpregu.1992.263.6.r1260
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发表时间：
1992-12-01
影响因子：
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通讯作者：
CHEN, YF
中科院分区：
文献类型：
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作者：
ELTON, TS;OPARIL, S;CHEN, YF
目前的研究验证了这一假设，即暴露于缺氧增强内皮素-1（ET-1）的基因表达和升高循环ET-1水平的大鼠。将大鼠暴露于常压缺氧（10%O2）或室内空气中24或48 h。用放射免疫法测定动脉血ET-1。采用狭缝杂交技术检测肺、左、右心房、左、右心室、肾、脾、肝、脑、肺动脉主干和胸主动脉的总RNA中ET-1基因转录水平。用不与ET-2或ET-3的mRNA交叉杂交的0.5 kb大鼠prepro ET-1 cDNA探测印迹。血浆ET-1水平在缺氧24小时（10.03 ± 2.33 pg/ml）和48小时（14.02 ± 3.44 pg/ml）显著高于空气对照组（4.14 ± 0.66 pg/ml）。缺氧48 h后，肺和右心房ET-1 mRNA水平显著升高（2倍），全身血管床灌注的器官未见变化。这些结果表明，缺氧引起的循环ET-1水平的增加主要是肺源性的。肺内皮细胞产生的ET-1的旁分泌作用可能是低氧性肺动脉高压的原因之一。
The current study tested the hypothesis that exposure to hypoxia enhances endothelin-1 (ET-1) gene expression and elevates circulating ET-1 levels in the rat. Rats were exposed to normobaric hypoxia (10% O2) or room air for 24 or 48 h. ET-1 in arterial blood was measured by radioimmunoassay. ET-1 gene transcript levels were measured by the slot blot technique on total RNA isolated from lung, right and left atria, right and left ventricles, kidney, spleen, liver, brain, main trunk of pulmonary artery, and thoracic aorta. Blots were probed with a 0.5 kb rat prepro ET-1 cDNA that does not cross-hybridize with mRNA for ET-2 or ET-3. Plasma ET-1 levels were increased significantly at 24 (10.03 +/- 2.33 pg/ml) and 48 h (14.02 +/- 3.44 pg/ml) of hypoxia compared with air controls (4.14 +/- 0.66 pg/ml). ET-1 mRNA levels were increased significantly (2-fold) in lung and right atrium after 48 h of hypoxia; no change was seen in organs perfused by the systemic vascular bed. These findings suggest that the hypoxia-induced increase in circulating ET-1 levels is mainly of pulmonary origin. A paracrine effect of ET-1 produced by lung endothelial cells could account for hypoxic pulmonary hypertension.