Davidge S T, Baker P N, Roberts J M
Magee-Womens Research Institute, University of Pittsburgh, Pennsylvania 15213, USA.
Am J Physiol. 1995 Sep;269(3 Pt 2):H1106-12. doi: 10.1152/ajpheart.1995.269.3.H1106.
Endothelial cell function is proposed to be altered by a factor(s) in the maternal circulation of women with the pregnancy disorder preeclampsia. Our initial hypothesis was that in preeclampsia, such factor(s) would reduce synthesis of nitric oxide (NO) by endothelial cells. However, we previously observed increased NO synthase activity in endothelial cells exposed to plasma from preeclamptic women. This study tested whether exposing cells to plasma from preeclamptic women increased transcription and/or translation of endothelial NO synthase. Cultured bovine coronary microvascular endothelial cells were exposed to 2% plasma from patients with preeclampsia and patients with uncomplicated pregnancies. Nitrite production was greater in endothelial cells exposed to plasma from preeclamptic women (8.97 +/- 0.54 vs. 6.39 +/- 0.59 nmol nitrites.10(6) cells-1 x 24 h-1; P < 0.05). Similarly, endothelial NO synthase mass as measured by Western immunoblotting was significantly increased (20,980 +/- 1,406 vs. 15,047 +/- 1,003 absorbancy units; P < 0.02). There was no detectable difference in mRNA for endothelial NO synthase. However, actinomycin (3 micrograms/ml), a transcription inhibitor, significantly decreased nitrite production only in cells exposed to plasma from preeclamptic women (5.28 +/- 0.52 vs. 3.56 +/- 0.36 nmol.10(6) cells-1 x 24 h-1, P < 0.05). These findings indicate a regulation of the "constitutive" isoform of NO synthase by factor(s) in the blood of preeclamptic women, which may have significance in this pathological condition of pregnancy.
有研究提出，患有先兆子痫这一妊娠疾病的女性，其母体内循环中的某种因素会改变内皮细胞功能。我们最初的假设是，在先兆子痫中，这种因素会减少内皮细胞一氧化氮（NO）的合成。然而，我们之前观察到，暴露于先兆子痫女性血浆中的内皮细胞，其NO合酶活性增加。本研究检测了将细胞暴露于先兆子痫女性血浆中是否会增加内皮型NO合酶的转录和/或翻译。将培养的牛冠状动脉微血管内皮细胞暴露于先兆子痫患者和无并发症妊娠患者的2%血浆中。暴露于先兆子痫女性血浆的内皮细胞中亚硝酸盐生成量更高（8.97±0.54对6.39±0.59 nmol亚硝酸盐·10⁶细胞⁻¹×24小时⁻¹；P<0.05）。同样，通过Western免疫印迹法测得的内皮型NO合酶质量显著增加（20980±1406对15047±1003吸光度单位；P<0.02）。内皮型NO合酶的mRNA没有可检测到的差异。然而，转录抑制剂放线菌素（3微克/毫升）仅在暴露于先兆子痫女性血浆的细胞中显著降低了亚硝酸盐生成量（5.28±0.52对3.56±0.36 nmol·10⁶细胞⁻¹×24小时⁻¹，P<0.05）。这些发现表明，先兆子痫女性血液中的某种因素对NO合酶的“组成型”同工型有调节作用，这可能在这种妊娠病理状况中具有重要意义。
