Dupuis J, Cernacek P, Tardif J C, Stewart D J, Gosselin G, Dyrda I, Bonan R, Crépeau J
Department of Medicine, Montreal Heart Institute, Quebec, Canada.
Am Heart J. 1998 Apr;135(4):614-20. doi: 10.1016/s0002-8703(98)70276-5.
Pulmonary hypertension (PHT) is associated with increased endothelin-1 (ET-1) levels that correlate with the severity of the disease. The pulmonary circulation is an important site for ET-1 metabolism and may modulate plasma ET-1 through an increase in production, a reduction in removal, or a combination of both. We measured and compared pulmonary metabolism of circulating ET-1 in controls and in patients with PHT.
The indicator-dilution technique was combined with measurements of ET-1 levels to quantify pulmonary metabolism of ET-1 in controls (n = 13) and in patients with PHT (n = 17). ET-1 levels doubled in PHT (p < 0.05) and, although there was no difference between aortic and pulmonary artery levels in controls (0.68+/-0.09 and 0.61+/-0.08 pg/ml, respectively, p = 0.22), they tended to be higher in PHT (1.23+/-0.26 vs 1.07+/-0.19 pg/ml, p = 0.08). Pulmonary extraction of tracer iodine-125-ET-1 was reduced from 47%+/-2.0% in the controls to 34%+/-3.6% in PHT (p = 0.005) and inversely correlated with the severity of pulmonary hypertension (r = -0.524, p = 0.03). Consequently, circulating ET-1 clearance was reduced by PHT from 1424+/-77 ml/min to 892+/-119 ml/min (p < 0.001). Pulmonary production of circulating ET-1 (in picograms per minute) was not different but the quantity of ET-1 that survives passage through the lungs was increased by PHT (1860+/-359 pg/min vs 992+/-152 pg/min, p = 0.037).
PHT is associated with a reduced pulmonary clearance of ET-1 that contributes to the increase in circulating levels.
肺动脉高压（PHT）与内皮素 -1（ET-1）水平升高相关，且该水平与疾病严重程度相关。肺循环是ET-1代谢的重要部位，可能通过增加生成、减少清除或两者兼而有之来调节血浆ET-1水平。我们测量并比较了对照组和PHT患者循环中ET-1的肺代谢情况。
将指示剂稀释技术与ET-1水平测量相结合，以量化对照组（n = 13）和PHT患者（n = 17）中ET-1的肺代谢。PHT患者的ET-1水平翻倍（p < 0.05），尽管对照组主动脉和肺动脉水平之间无差异（分别为0.68±0.09和0.61±0.08 pg/ml，p = 0.22），但PHT患者中这些水平往往更高（1.23±0.26对1.07±0.19 pg/ml，p = 0.08）。示踪剂碘 -125-ET-1的肺摄取率从对照组的47%±2.0%降至PHT患者的34%±3.6%（p = 0.005），且与肺动脉高压严重程度呈负相关（r = -0.524，p = 0.03）。因此，PHT使循环中ET-1清除率从1424±77 ml/min降至892±119 ml/min（p < 0.001）。循环中ET-1的肺生成量（以皮克/分钟计）无差异，但PHT使通过肺后存活的ET-1量增加（1860±359 pg/min对992±152 pg/min，p = 0.037）。
PHT与ET-1肺清除率降低相关，这导致循环水平升高。
