Dehydroepiandrosterone (DHEA) prevents and reverses chronic hypoxic pulmonary hypertension
Dehydroepiandrosterone (DHEA) prevents and reverses chronic hypoxic pulmonary hypertension
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DOI：
10.1073/pnas.1633724100
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发表时间：
2003-08-05
影响因子：
11.1
通讯作者：
Baulieu, EE
中科院分区：
文献类型：
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作者：
Bonnet, S;Dumas-de-La-Roque, E;Baulieu, EE
在大鼠慢性缺氧肺动脉高压模型（7-21 天）中研究肺动脉（PA）高血压。口服脱氢表雄酮 (DHEA)（每隔一天 30 mg/kg）后，PA 压力升高（通过导管插入术测量）、心脏右心室肥大（通过超声心动图测定）和 PA 重塑（通过组织学评估）几乎完全得到预防。此外，在高血压大鼠中，口服或血管内注射（颈静脉）DHEA 可迅速降低 PA 高血压。在 PA 平滑肌细胞中，DHEA 降低了细胞内钙的水平（通过显微荧光光度法测量）。 DHEA 的作用似乎涉及大电导 Ca2+ 激活钾通道 (BKCa) 依赖性刺激机制，在功能和表达水平（等长收缩和蛋白质印迹）上，通过氧化还原依赖性途径。电压门控钾 (Kv) 通道也可能参与其中，因为拮抗剂 4-氨基-吡啶阻断了部分 DHEA 作用。讨论了结果可能的病理生理学和治疗意义。
Pulmonary artery (PA) hypertension was studied in a chronic hypoxic-pulmonary hypertension model (7-21 days) in the rat. Increase in PA pressure (measured by catheterism), cardiac right ventricle hypertrophy (determined by echocardiography), and PA remodeling (evaluated by histology) were almost entirely prevented after oral dehydroepiandrosterone (DHEA) administration (30 mg/kg every alternate day). Furthermore, in hypertensive rats, oral administration, or intravascular injection (into the jugular vein) of DHEA rapidly decreased PA hypertension. In PA smooth muscle cells, DHEA reduced the level of intracellular calcium (measured by microspectrofluorimetry). The effect of DHEA appears to involve a large conductance Ca2+-activated potassium channel (BKCa)-dependent stimulatory mechanism, at both function and expression levels (isometric contraction and Western blot), via a redox-dependent pathway. Voltage-gated potassium (Kv) channels also maybe involved because the antagonist 4-amino-pyridine blocked part of the DHEA effect. The possible pathophysiological and therapeutic significance of the results is discussed.