Jovanović A, Jovanović S, Grbović L
Department of Clinical Pharmacology, Pharmacology and Toxicology, School of Medicine, Belgrade, Yugoslavia.
Hum Reprod. 1997 Aug;12(8):1805-9. doi: 10.1093/humrep/12.8.1805.
Recently, strong evidence has suggested that nitric oxide (NO) synthesis is significantly increased in the uterine artery during pregnancy, which may mediate the increased blood flow to the uterus that is characteristic of pregnancy. We therefore investigated the nature of the mediators of acetylcholine (ACh)-induced relaxation in pregnant guinea-pig uterine arterial rings. ACh (0.1 nM to 60 microM) induced endothelium-dependent relaxation of phenylephrine-precontracted pregnant guinea-pig uterine artery. N(G)-monomethyl-L-arginine (3-30 microM) antagonized the effect of ACh, with suppression of maximal ACh-induced relaxation, in a concentration-dependent manner. The inhibition of relaxation by N(G)-monomethyl-L-arginine (10 microM) was significantly overcome by L-arginine (10 microM), but not by D-arginine (100 microM). On the contrary, the administration of indomethacin (10 microM) and diethylcarbamazine (100 microM) did not modify the relaxation of guinea-pig uterine artery induced by ACh. The ACh-evoked relaxation was unaltered when K+-rich Krebs-Ringer bicarbonate solution was used to induce tone instead of phenylephrine, or when a nonselective blocker of K+ channels, 4-aminopyridine (6 mM), was applied to phenylephrine-precontracted segments. It is concluded that the relaxation induced by ACh in pregnant guinea-pig uterine artery can be explained entirely by the release of NO from vascular endothelial cells, without involvement of other endothelium-derived relaxing factors, similar to that previously reported for non-pregnant guinea-pig uterine artery. Thus, it seems that increased activity of NO synthase during pregnancy is without significant influence on the ACh action on uterine artery.
最近，有力证据表明，孕期子宫动脉中一氧化氮（NO）的合成显著增加，这可能介导了孕期子宫血流量增加这一特征性变化。因此，我们研究了乙酰胆碱（ACh）诱导妊娠豚鼠子宫动脉环舒张的介质性质。ACh（0.1 nM至60 μM）可诱导苯肾上腺素预收缩的妊娠豚鼠子宫动脉产生内皮依赖性舒张。N（G）-单甲基-L-精氨酸（3 - 30 μM）以浓度依赖性方式拮抗ACh的作用，抑制ACh诱导的最大舒张。L-精氨酸（10 μM）可显著克服N（G）-单甲基-L-精氨酸（10 μM）对舒张的抑制作用，而D-精氨酸（100 μM）则不能。相反，吲哚美辛（10 μM）和乙胺嗪（100 μM）的给药并未改变ACh诱导的豚鼠子宫动脉舒张。当用富含K +的 Krebs-Ringer碳酸氢盐溶液代替苯肾上腺素诱导张力时，或当对苯肾上腺素预收缩节段应用K +通道非选择性阻滞剂4-氨基吡啶（6 mM）时，ACh诱发的舒张未改变。结论是，ACh诱导的妊娠豚鼠子宫动脉舒张完全可以由血管内皮细胞释放NO来解释，而不涉及其他内皮源性舒张因子，这与先前报道的非妊娠豚鼠子宫动脉情况相似。因此，孕期NO合酶活性增加似乎对ACh对子宫动脉的作用没有显著影响。
