Motta A B, Chaud M A, de Gimeno M F
Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Buenos Aires, Argentina.
Prostaglandins Leukot Essent Fatty Acids. 1998 May;58(5):333-8. doi: 10.1016/s0952-3278(98)90068-0.
We explored the role of endogenous nitric oxide (NO) in the spontaneous motility of uterine tissue from pseudopregnant (psp) rats and the correlation between this action and the uterotonic prostaglandin (PG) E production. We worked in the early psp (on day 5 of psp), and in late psp (on day 8 and day 9). Treatment with N(G)-monomethyl-L-arginine L-NMMA (300 microM), a competitive nitric oxide synthase (NOS) inhibitor, did not modify isometric developed tension (IDT) and frequency of contractions (FC) on day 5 of psp; on day 8, tissue pretreated with L-NMMA showed an increase in the IDT and FC compared with controls, while on day 9 of psp, both IDT and FC showed a lower stability after treatment with the inhibitor. These data suggest that NO modulates uterine motility on day 8 (decreasing it) and on day 9 of psp (enhancing it). We also evaluated the total NOS activity and that of its isoforms at the three times mentioned, demonstrating that total NOS activity was higher on day 5 of psp and decreased with psp development. On day 5 of psp, calcium-dependent and calcium-independent NOS each forms around 50% of total NOS activity. On day 8 of psp, the calcium-dependent was the predominant NOS form, while on day 9 of psp, the uterine tissue showed a higher calcium-independent form of the enzyme. In view of the fact that we found an inhibitor effect of the endogenous NO in uterine contractility on day 8 of psp and an inverse action on day 9 of psp (enhancing uterine contractility), we suggest that the NOS calcium-dependent form could be responsible for uterine contractility in psp rats. Finally, we evaluated the relationship between endogenous NO and PGE production. We observed that on days 5 and 8 of psp, the L-NMMA (300 microM) treatment did not affect PGE production, but on day 9 of psp, the preincubation with the NOS inhibitor diminished PGE synthesis, suggesting that at this time endogenous NO can upregulate uterine PGE production. These results confirm that NO can modulate uterine motility by means of PGE production. In summary, we suggest that in uterine tissue from psp rats, the NO system can alternatively decrease or increase uterine contractions, this last effect by enhancing uterine PGE synthesis.
我们探讨了内源性一氧化氮（NO）在假孕（psp）大鼠子宫组织自发运动中的作用，以及该作用与子宫收缩性前列腺素（PG）E产生之间的相关性。我们分别在假孕早期（假孕第5天）和晚期（假孕第8天和第9天）进行研究。用竞争性一氧化氮合酶（NOS）抑制剂N(G)-单甲基-L-精氨酸L-NMMA（300微摩尔）处理，在假孕第5天并未改变等长收缩张力（IDT）和收缩频率（FC）；在第8天，用L-NMMA预处理的组织与对照组相比，IDT和FC增加，而在假孕第9天，用抑制剂处理后，IDT和FC的稳定性均降低。这些数据表明，NO在假孕第8天（降低子宫运动）和第9天（增强子宫运动）调节子宫运动。我们还评估了上述三个时间点的总NOS活性及其同工酶活性，结果表明，总NOS活性在假孕第5天较高，并随假孕进程降低。在假孕第5天，钙依赖性和钙非依赖性NOS各自约占总NOS活性的50%。在假孕第8天，钙依赖性NOS是主要形式，而在假孕第9天，子宫组织显示出较高的钙非依赖性NOS形式。鉴于我们发现内源性NO在假孕第8天对子宫收缩有抑制作用，而在假孕第9天有相反作用（增强子宫收缩），我们认为钙依赖性NOS形式可能是假孕大鼠子宫收缩的原因。最后，我们评估了内源性NO与PGE产生之间的关系。我们观察到，在假孕第5天和第8天，L-NMMA（300微摩尔）处理不影响PGE产生，但在假孕第9天，用NOS抑制剂预孵育会减少PGE合成，这表明此时内源性NO可上调子宫PGE产生。这些结果证实，NO可通过PGE产生来调节子宫运动。总之，我们认为在假孕大鼠的子宫组织中，NO系统可交替降低或增加子宫收缩，后一种作用是通过增强子宫PGE合成实现的。
