Cacoub P, Dorent R, Nataf P, Carayon A, Riquet M, Noe E, Piette J C, Godeau P, Gandjbakhch I
Department of Internal Medicine, CHU Pitié-Salpétrière, Paris, France.
Cardiovasc Res. 1997 Jan;33(1):196-200. doi: 10.1016/s0008-6363(96)00189-7.
Pulmonary hypertension (PH) is characterized by an increase in vascular tone and an abnormal proliferation of muscle cells in the walls of pulmonary arteries. Recent studies have found high plasma endothelin-1 (ET-1) concentrations in patients with PH. This study was conducted to assess whether elevated circulating ET-1 levels in PH really reflect excessive local pulmonary production.
We prospectively studied ET-1 concentration in lung specimens from 6 control subjects and 13 patients with severe PH referred for lung or heart-lung transplantation (6 patients had primary PH and 7 PH secondary to congenital heart defect). Endothelin-like immunoreactivity (ET-LI) was measured in plasma and lung tissue, using a radioimmunoassay, after ET-1 extraction. Reverse-phase high-performance liquid chromatography was also performed.
Peripheral venous plasma ET-LI concentrations in patients with PH, whatever the cause, were greater than those in controls (10.7 +/- 0.8 vs 5.3 +/- 0.7 pg/ml; P < 0.0005). Pulmonary ET-LI was significantly higher in patients with PH, irrespective of its cause, than in controls (25.2 +/- 5.1 vs 8.1 +/- 1.1 pg/mg, P < 0.03). ET-LI pulmonary concentrations were slightly higher in Eisenmenger than in primary PH, but this was not significant (27.1 +/- 8.6 vs 22.8 +/- 5.4 pg/mg). Linear regression analysis indicated a small but significant correlation between ET-LI pulmonary concentrations and pulmonary vascular resistance in the patients with PH (r = 0.38; P = 0.047). In each case, HPLC separation of ET indicated that most of the immuno-reactivity was detected in the same fraction as ET-1.
The striking increase in ET-1 pulmonary concentration provides new evidence that excessive local pulmonary ET-1 production may contribute to the vascular abnormalities of pulmonary hypertension.
肺动脉高压（PH）的特征是血管张力增加以及肺动脉壁肌肉细胞异常增殖。最近的研究发现，PH患者血浆内皮素-1（ET-1）浓度升高。本研究旨在评估PH患者循环中ET-1水平升高是否真的反映了肺局部的过度产生。
我们前瞻性地研究了6名对照受试者和13名因肺或心肺移植而转诊的重度PH患者（6例为原发性PH，7例为先天性心脏病继发的PH）肺标本中的ET-1浓度。在提取ET-1后，采用放射免疫分析法测定血浆和肺组织中的内皮素样免疫反应性（ET-LI）。还进行了反相高效液相色谱分析。
无论病因如何，PH患者外周静脉血浆ET-LI浓度均高于对照组（10.7±0.8 vs 5.3±0.7 pg/ml；P<0.0005）。无论病因如何，PH患者的肺ET-LI均显著高于对照组（25.2±±5.1 vs 8.1±1.1 pg/mg，P<0.03）。艾森曼格综合征患者的ET-LI肺浓度略高于原发性PH患者，但差异不显著（27.1±8.6 vs 22.8±5.4 pg/mg）。线性回归分析表明，PH患者的ET-LI肺浓度与肺血管阻力之间存在小但显著的相关性（r = 0.38；P = 0.047）。在每种情况下，ET的HPLC分离表明，大多数免疫反应性在与ET-1相同的馏分中检测到。
ET-1肺浓度的显著升高提供了新的证据，表明肺局部ET-1的过度产生可能导致肺动脉高压的血管异常。
