Weiner C P, Knowles R G, Moncada S
Wellcome Research Laboratories, Beckenham, United Kingdom.
Am J Obstet Gynecol. 1994 Sep;171(3):838-43. doi: 10.1016/0002-9378(94)90108-2.
We have previously demonstrated that calcium-dependent nitric oxide synthase is induced by estrogen and that by the end of pregnancy nitric oxide synthase of both endothelial and neuronal origin is increased in various maternal tissues. This rise in activity may be crucial for the alterations in muscle activity necessary for a successful pregnancy. If so, the increase in nitric oxide synthase activity must occur early in gestation.
We tested the hypothesis that pregnancy increases nitric oxide synthase activity early in gestation by measuring in heart, kidney, skeletal muscle, and esophagus of time-mated guinea pigs the conversion by nitric oxide synthase of carbon 14-labeled L-arginine to carbon 14-labeled citrulline and the concentration of cyclic guanosine monophosphate, the second messenger of nitric oxide.
Calcium-dependent nitric oxide synthase activity was increased twofold to fourfold by pregnancy in each tissue examined. The rise began by 0.14 gestation (9 of 63 +/- 2 days) and reached a plateau by 0.30 gestation (19 days), which was then maintained until term. The treatment of pregnant animals with tamoxifen decreased nitric oxide synthase activity to nonpregnant values in the heart, where tamoxifen is an estrogen receptor antagonist, but not in kidney, skeletal muscle, and esophagus. Cyclic guanosine monophosphate also rose progressively in each tissue studied until about 0.70 gestation before declining in skeletal muscle, kidney, and heart. It remained elevated in the esophagus.
These studies demonstrate that nitric oxide synthase activity in maternal tissues rises early in pregnancy and is associated with an increase in cyclic guanosine monophosphate, the second messenger of nitric oxide. These findings are consistent with the hypothesis that an increase in nitric oxide synthase plays a role in smooth muscle adaptations of pregnancy.
我们之前已经证明，钙依赖性一氧化氮合酶可被雌激素诱导，并且在妊娠末期，内皮细胞和神经元来源的一氧化氮合酶在母体的各种组织中均有增加。这种活性的升高对于成功妊娠所需的肌肉活动改变可能至关重要。如果是这样，一氧化氮合酶活性的增加必须在妊娠早期就发生。
我们通过测量同期交配的豚鼠心脏、肾脏、骨骼肌和食管中一氧化氮合酶将碳14标记的L-精氨酸转化为碳14标记的瓜氨酸的转化率以及一氧化氮的第二信使环磷酸鸟苷的浓度，来检验妊娠在妊娠早期增加一氧化氮合酶活性这一假设。
在所检查的每个组织中，妊娠使钙依赖性一氧化氮合酶活性增加了两倍至四倍。这种升高在妊娠0.14时（63±2天中的9天）开始，在妊娠0.30时（19天）达到平台期，然后一直维持到足月。用他莫昔芬治疗怀孕动物，可使心脏中的一氧化氮合酶活性降至未怀孕时的水平，他莫昔芬在心脏中是一种雌激素受体拮抗剂，但在肾脏、骨骼肌和食管中则不然。在所研究的每个组织中，环磷酸鸟苷也逐渐升高，直到妊娠约0.70时，然后在骨骼肌、肾脏和心脏中下降。它在食管中仍保持升高。
这些研究表明，母体组织中的一氧化氮合酶活性在妊娠早期升高，并与一氧化氮的第二信使环磷酸鸟苷的增加有关。这些发现与一氧化氮合酶增加在妊娠平滑肌适应中起作用的假设一致。
