Cracowski J L, Cracowski C, Bessard G, Pepin J L, Bessard J, Schwebel C, Stanke-Labesque F, Pison C
Laboratoire de Pharmacologie, and Département de Médecine Aiguë Spécialisée, Grenoble University Hospital, Grenoble, France.
Am J Respir Crit Care Med. 2001 Sep 15;164(6):1038-42. doi: 10.1164/ajrccm.164.6.2104033.
Isoprostanes are chemically stable lipid peroxidation products of arachidonic acid, the quantification of which provides a novel approach to the assessment of oxidative stress in vivo. The main objective of this study was to quantify the urinary levels of isoprostaglandin F(2alpha) type III (iPF(2alpha)-III), an F(2)-isoprostane, in patients with pulmonary hypertension (PHT) in comparison with healthy controls. The secondary objective was to test whether baseline iPF(2alpha)-III levels correlate to the reversibility of pulmonary hypertension in response to inhaled NO challenge. Urinary iPF(2alpha)-III levels were measured by gas chromatography-mass spectrometry in 25 patients with PHT, 14 of whom were investigated for response to inhaled NO challenge. Urinary iPF(2alpha)-III levels in PHT patients (225 +/- 27 pmol/mmol creatinine) were 2.3 times as high as in controls (97 +/- 7 pmol/mmol creatinine, p < 0.001). The mean pulmonary arterial pressure variation and the pulmonary vascular resistance variation in response to inhaled NO were correlated to basal iPF(2alpha)-III levels. This study shows that oxidative stress is increased in patients with pulmonary hypertension. Furthermore, iPF(2alpha)-III levels inversely correlate to pulmonary vasoreactivity. These observations are consistent with the hypothesis that free radical generation is involved in PHT pathogenesis.
异前列腺素是花生四烯酸的化学稳定的脂质过氧化产物，其定量分析为体内氧化应激评估提供了一种新方法。本研究的主要目的是定量测定肺动脉高压（PHT）患者尿中F2-异前列腺素III型（iPF(2α)-III）的水平，并与健康对照者进行比较。次要目的是检测基线iPF(2α)-III水平是否与吸入一氧化氮激发试验后肺动脉高压的可逆性相关。采用气相色谱-质谱法测定了25例PHT患者的尿iPF(2α)-III水平，其中14例患者接受了吸入一氧化氮激发试验。PHT患者尿iPF(2α)-III水平（225±27 pmol/mmol肌酐）是对照组（97±7 pmol/mmol肌酐，p < 0.001）的2.3倍。吸入一氧化氮后平均肺动脉压变化和肺血管阻力变化与基础iPF(2α)-III水平相关。本研究表明，肺动脉高压患者氧化应激增加。此外，iPF(2α)-III水平与肺血管反应性呈负相关。这些观察结果与自由基生成参与PHT发病机制的假说一致。
