Similar changes have also been reported in the human, indicating that the NO system is a potentially important system for uterine relaxation during pregnancy.
Studies on the use of NO donors as tocolytics in the threatened preterm labor in women have been limited to very few. In 1994, transdermal patches of GTN were reported to prolong pregnancy for a mean of 59 days in a group of 13 women. In 1996, in another group of 10 women, pregnancy was prolonged for a mean of 46.2 days. The effects of GTN appeared to be due to reductions in uterine contractions in these preterm labor women. It is unknown from these studies whether NO donors are superior to other tocolytics; however, the side effects appear to be less severe.
It is unclear if the intact uterine NO system is critical for maintaining uterine quiescence during normal pregnancy. Studies in the rat and sheep indicate that inhibition of NO synthesis prior to term does not result in parturition; however, this does occur in mice. It is possible that NO may interact with other uterotonins and that the resultant effects may depend on these interactions. Moreover, uterine NO synthesis has been shown to be regulated by estradiol and progesterone, key hormones in pregnancy. Progesterone not only enhances NO synthase expression and NO synthesis in rat uterus, but also enhances NO-induced uterine relaxation. On the other hand, antiprogesterones decrease NO synthase enzymes, inhibit NO synthesis, and reduce uterine relaxation responsiveness to NO. Furthermore, inhibition of NO synthesis during pregnancy in the presence of a low dose of antiprogesterone leads to preterm labor in the rat. On the other hand, NO donors prevented prostaglandin F2α-induced preterm labor in the rat. These studies in the rat suggest that NO may interact with other uterotonins in the maintenance of uterine quiescence during pregnancy. In conclusion, uterine NO system may play a role in maintaining uterine quiescence during pregnancy, and perturbation of this system could facilitate preterm parturition.