EVIDENCE AGAINST A PATHOGENETIC ROLE FOR ENDOTHELIN IN PREECLAMPSIA
EVIDENCE AGAINST A PATHOGENETIC ROLE FOR ENDOTHELIN IN PREECLAMPSIA
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DOI：
10.1111/j.1471-0528.1992.tb14409.x
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发表时间：
1992-10-01
期刊：
影响因子：
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通讯作者：
REMUZZI, G
中科院分区：
文献类型：
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作者：
BENIGNI, A;ORISIO, S;REMUZZI, G
目的探讨胎盘或全身内皮素合成增加是否与子痫前期（妊娠期蛋白尿性高血压）发病有关，设计前瞻性观察研究，研究对象为19例子痫前期患者和10例健康孕妇。所有的人都在最后三个月。主要结果测量前原内皮素-1基因表达的北方印迹分析和生成的内皮素-1前体，大内皮素-1，内皮素亚型，即内皮素-1，2和3，进行了评估，在胎盘组织中的特定放射免疫分析。结果子痫前期患者胎盘组织中内皮素前体1基因表达及内皮素1、内皮素2、内皮素3的免疫反应阳性率与正常孕妇比较，差异有统计学意义（P < 0. 05）。血浆内皮素-1水平在先兆子痫和正常妊娠之间没有差异。与此相反，与正常孕妇相比，先兆子痫患者尿中内皮素-1的排泄量显著减少，这可能反映了肾合成的肽。这不是由于减少肾生成内皮素-1前体，因为尿排泄的大内皮素-1之间先兆子痫和正常妊娠没有差异。这些数据表明，增加肾内皮素-1分解在先兆子痫。结论内皮素是不可能发挥作用的发病机制先兆子痫。相反，增加的肾衰竭可能在限制其他血管活性因子对肾循环的负面影响方面发挥作用。
Objective To assess whether increased placental or systemic endothelin synthesis has a pathogenic role in pre-eclampsia (gestational proteinuric hypertension).Design Prospective observations study.Subjects 19 women with pre-eclampsia and 10 healthy pregnant women were studied. All were in the last trimester.Main outcome measures Preproendothelin-1 gene expression by Northern blot analysis and generation of endothelin-1 precursor, big-endothelin-1, and endothelin isoforms, namely endothelin-1, 2 and 3, were assessed by specific radioimmunoassays, in placental tissue. Plasma endothelin-1 levels and urinary excretion of big-endothelin-1 and endothelin-1 were measured.Results Placental preproendothelin-1 gene expression and immunoreactive big-endothelin-1 and endothelin-1, 2 and 3, were comparable in placental tissue from pre-eclamptic and normal pregnant women. Plasma levels of endothelin-1 did not differ between pre-eclamptic and normal pregnancies. In contrast, urinary excretion of endothelin-1, which is likely to reflect the renal synthesis of the peptide, was significantly decreased in pre-eclamptic, as compared with normal pregnant women. This was not due to a decreased renal generation of endothelin-1 pre-cursor, since urinary excretion of big-endothelin-1 did not differ between pre-eclamptic and normal pregnancies. These data suggest an increased renal endothelin-1 breakdown in pre-eclampsia.Conclusions Endothelin is unlikely to play a role in the pathogenesis of pre-eclampsia. Instead, an increased renal breakdown may have a role in limiting the negative effects of other vasoactive factors on the renal circulation.