Myatt L, Brewer A S, Langdon G, Brockman D E
Perinatal Research Institute, University of Cincinnati College of Medicine, OH 45267-0526.
Am J Obstet Gynecol. 1992 Jan;166(1 Pt 1):224-30. doi: 10.1016/0002-9378(92)91863-6.
We hypothesized that the endothelial-derived relaxing factor nitric oxide may contribute to low resting vascular tone and may attenuate vasoconstrictor action in the human fetal-placental circulation.
Isolated human placental cotyledons were dually perfused in vitro, and the effects of N-monomethyl-L-arginine and N-nitro-L-arginine (3 x 10(-4) mol/L), which are nonmetabolizable analogs of L-arginine, the substrate for nitric oxide synthase, on resting perfusion pressure and on the fetal-placental circulation preconstricted with U46619 (10(-8) mol/L) or endothelin-1 (10(-8) mol/L) were established. Responses before and after inhibition were compared by paired t test. The effects of glyceryl trinitrate (10(-6) mol/L), acetylcholine (10(-4) mol/L), the calcium ionophore A23187 (10(-6) mol/L), and histamine (10(-8) to 10(-4) mol/L) were also determined in the preconstricted fetal-placental circulation.
Both N-monomethyl-L-arginine and N-nitro-L-arginine (3 x 10(-4) mol/L) increased resting perfusion pressure (p less than 0.06), and N-nitro-L-arginine promptly and significantly increased perfusion pressure in the fetal-placental circulation preconstricted with U46619 (p less than 0.0004) or endothelin-1 (p less than 0.06). Nitric oxide generated by addition of glyceryl trinitrate (10(-6) mol/L) attenuated the vasoconstrictor effects of U46619 (p less than 0.026) or endothelin-1 (p less than 0.01). Neither acetylcholine nor the calcium ionophore A23187 had an effect on the fetal-placental circulation, whereas bradykinin further increased perfusion pressure. Histamine only relaxed the preconstricted preparations at concentrations (10(-6) to 10(-4) mol/L) above those shown to release nitric oxide in other systems.
The stimulus to nitric oxide generation in the fetal-placental circulation may be hydrodynamic. Nitric oxide appears to contribute to maintenance of basal vascular tone and to attenuate the actions of vasoconstrictors in this circulation.
我们推测内皮源性舒张因子一氧化氮可能有助于维持较低的静息血管张力，并可能减弱人胎儿-胎盘循环中的血管收缩作用。
将离体的人胎盘小叶进行体外双重灌注，观察一氧化氮合酶的底物L-精氨酸的非代谢类似物N-单甲基-L-精氨酸和N-硝基-L-精氨酸（3×10⁻⁴mol/L）对静息灌注压力以及对用U46619（10⁻⁸mol/L）或内皮素-1（10⁻⁸mol/L）预收缩的胎儿-胎盘循环的影响。通过配对t检验比较抑制前后的反应。还测定了硝酸甘油（10⁻⁶mol/L）、乙酰胆碱（10⁻⁴mol/L）、钙离子载体A23187（10⁻⁶mol/L）和组胺（10⁻⁸至10⁻⁴mol/L）在预收缩的胎儿-胎盘循环中的作用。
N-单甲基-L-精氨酸和N-硝基-L-精氨酸（3×10⁻⁴mol/L）均增加了静息灌注压力（p<0.06），N-硝基-L-精氨酸迅速且显著地增加了用U46619（p<0.0004）或内皮素-1（p<0.06）预收缩的胎儿-胎盘循环中的灌注压力。添加硝酸甘油（10⁻⁶mol/L）产生的一氧化氮减弱了U46619（p<0.026）或内皮素-1（p<0.01）的血管收缩作用。乙酰胆碱和钙离子载体A23187对胎儿-胎盘循环均无影响，而缓激肽进一步增加了灌注压力。组胺仅在高于其他系统中显示能释放一氧化氮的浓度（10⁻⁶至10⁻⁴mol/L）时才使预收缩的制剂舒张。
胎儿-胎盘循环中一氧化氮生成的刺激因素可能是流体动力学因素。一氧化氮似乎有助于维持基础血管张力，并减弱该循环中血管收缩剂的作用。
