Involvement of s-nitrosylation on the effect of nitric oxide and its production in rat placenta

我们研究了一氧化氮（NO）在大鼠胎盘血管内皮生长因子（VEGF）表达中的作用。L-NAME是一种一氧化氮合酶（NOS）抑制剂，在妊娠日（GD） 15.5献祭前6-24 h持续输注于妊娠大鼠体内。通过NO捕获和电子顺磁共振谱监测，NO产量下降到控制水平的15%左右。L-NAME治疗后VEGF表达暂时降低，24 h后恢复正常，而缺氧诱导因子（HIF-1a）和诱导型NOS （iNOS）表达升高。L-NAME与iNOS诱导剂脂多糖共同作用6 h后，VEGF在胎盘组织中的表达显著降低。这些结果表明，NO在体内和体外诱导大鼠胎盘中VEGF的表达，表明NO和VEGF通过HIF-1a相互作用维持了NO的峰值生成。

We examined the role of nitric oxide (NO) in vascular endothelial growth factor (VEGF) expression in the rat placenta. A nitric oxide synthase (NOS) inhibitor, L-NAME was constantly infused into pregnant rats 6-24 h before sacrifice on gestational day (GD) 15.5. NO production declined to about 15% of the control level as monitored by NO trapping and electron paramagnetic resonance spectroscopy. VEGF expression was temporally decreased by L-NAME, but recovered to normal levels after 24 h of treatment, whereas hypoxia inducible factor (HIF-1a and inducible NOS (iNOS) expression increased. VEGF expression decreased significantly in placental explants after 6 h of co-treatment with L-NAME and lipopolysaccharide, an iNOS inducer. These results indicate that NO induce VEGF expression in vivo and in vitro in the rat placenta, suggesting that peaked NO production was maintained by a reciprocal relationship between NO and VEGF via HIF-1a.