Flow-induced pressure differentially regulates endothelin-1, urotensin II, adrenomedullin, and relaxin in pulmonary vascular endothelium
Flow-induced pressure differentially regulates endothelin-1, urotensin II, adrenomedullin, and relaxin in pulmonary vascular endothelium
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DOI：
10.1006/bbrc.2001.5946
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发表时间：
2001-11-23
影响因子：
3.1
通讯作者：
Stangl, K
中科院分区：
文献类型：
--
作者：
Dschietzig, T;Richter, C;Stangl, K
我们假设肺血管压力升高——充血性心力衰竭的特征之一——直接调节肺内皮血管收缩剂（内皮素-1，尿紧张素II）和血管舒张剂（肾上腺髓质素，松弛素）。为此，我们在一个新的流室模型中对肺动脉内皮细胞施加不同的剪切应力（17、29和46 dyn/cm(2)），分别处于低和高水平的下游压力（10和30 mm Hg）下。施加超过16小时的高压会在所有剪切水平上增加内皮素-1的基因表达和肽分泌，而肾上腺髓质素的分泌则通过其清除受体的表达减少而增加。相反，尿紧张素II前mRNA和尿紧张素II肽随着血压升高而降低，松弛素不受影响。这是首次发现压力是肺血管内皮合成介质的关键调节因子。压力诱导的介质调节可能代表继发性肺动脉高压发展的早期事件。(C) 2001学术出版社。
We hypothesized that increased pulmonary vascular pressure-one of the characteristics of congestive heart failure-directly regulates pulmonary endothelial vasoconstrictors (endothelin-1, urotensin II) and vasodilators (adrenomedullin, relaxin). To this end, we subjected pulmonary artery endothelial cells in a novel flow-chamber model to different shear stresses (17, 29, and 46 dyn/cm(2)) at low and elevated levels of downstream pressure (10 and 30 mm Hg). Application of elevated pressure over 16 h increased gene expression and peptide secretion of endothelin-1 at all shear levels, whereas secretion of adrenomedullin rose via decreased expression of its clearance receptor. In contrast, preprourotensin II mRNA and urotensin II peptide decreased in response to elevated pressure, and relaxin remained unaffected. This is the first study to identify pressure as key regulator of mediator synthesis by pulmonary vascular endothelium. Pressure-induced mediator regulation may represent an early event in the development of secondary pulmonary hypertension. (C) 2001 Academic Press.