The role of nitric oxide on uterine contraction at preterm

我们通过体外和体内实验证明了妊娠大鼠子宫中存在L-精氨酸-NO-cGMP途径。一氧化氮在妊娠中期抑制自发性子宫收缩，但在足月时不抑制，表明具有胎龄依赖性抑制作用。钙依赖性钾通道开放剂对离体大鼠子宫环自发收缩活动的抑制作用具有胎龄依赖性不应性，但三磷酸腺苷依赖性钾通道开放剂对子宫环自发收缩活动的抑制作用则无此作用。一氧化氮通过开放孕鼠子宫肌层钙依赖性钾通道抑制子宫收缩。对一氧化氮的不敏感性可能是由于钙依赖性钾通道开放的可能性或数量减少所致。胎盘组织的存在增强了自发释放一氧化氮的药物对子宫收缩的抑制作用，如二乙胺-一氧化氮，但不增强硝酸甘油对子宫收缩的抑制作用，硝酸甘油需要代谢转化才能释放一氧化氮。妊娠22-26周血浆NO代谢产物浓度显著高于非妊娠妇女，但随着妊娠的进行，血浆NO代谢产物浓度略有下降。早产患者血浆NO代谢产物浓度低于同孕周正常孕妇。因此，NO产物减少可能是早产的原因之一，提示NO在维持妊娠中期子宫静止中起重要作用。足月时子宫对NO的舒张反应性降低可能在分娩的开始中起作用。一氧化氮供体药物可能对抑制早产非常有效。

We demonstrated that an L-arginine-NO-cGMP pathway exists in pregnant rat uterus, through in vitro and in vivo experiments. Nitric oxide inhibits spontaneous contractions in rate uterus at midgestation but not at term, demonstrating gestational age-dependent inhibition. There is gestational age-dependent refractoriness to calcium-dependent potassium but not adenosine triphosphate-dependent potassium channel opener-induced inhibition of spontaneous contractile activity of isolated rat uterine rings. Nitric oxide inhibits uterine contractions by opening of calcium-dependent potassium channels in pregnant rat myometrium. Refractoriness to nitric oxide toward term may result from decreased probability to open or number of calcium-dependent potassium channels. The presence of placental tissue enhances inhibition of uterine contractility by agents that spontaneously release nitric oxide, such as diethylamine-nitric oxide, but no by nitroglycerin, which requires metabolic transformation for nitric oxide to be released. Refractoriness to nitric oxide near or at term does not depend on the presence or absence of placental tissue.The plasma NO metabolite concentration in 22-26 weeks of pregnancy was significantly higher than that of the non-pregnant women, although the plasma NO metabolite concentration was slightly decreased toward term. The plasma NO metabolite concentration in patients with preterm labor was lower than that of the normal pregnant women in same weeks of pregnancy. Therefore, decreasing NO products may be one of the causes of preterm birth.These studies suggest that NO has an important role in maintaining uterine quiescence at midgestation. A decrease in uterine relaxation responsiveness to NO at term may play a role in the initiation of labor. Nitric oxide donor drugs may be very effective in suppressing preterm labor.