Inhibitory effect of iloprost on the contractility of lower uterine segment myometrium from rhesus monkeys in normal-term and androstenedione-induced preterm labor.

OBJECTIVE: Iloprost, a combined EP(1) stimulatory and IP inhibitory receptor agonist, was tested in vitro on myometrium from the lower uterine segment of pregnant rhesus monkeys to compare its effects in spontaneous labor and in labor induced by the administration of androstenedione to the mother.

METHODS: Pregnant rhesus monkeys carrying fetuses of known gestational age were instrumented under halothane general anesthesia with femoral artery and vein catheters and uterine electromyogram leads. Experimental animals were infused with androstenedione from 139 days' gestation. Control animals were infused with intralipid vehicle from 139 days' gestation. Lower uterine segment myometrium was removed from control animals either before labor began (n = 6) or in spontaneous labor (n = 4) and from animals undergoing premature labor induced by androstenedione (n = 4). Myometrial contractility in response to iloprost was evaluated using a superfusion system in vitro.

RESULTS: Iloprost was inhibitory on myometrium obtained from the lower uterine segment from androstenedione-treated animals as well as vehicle-infused animals in spontaneous term labor. In contrast, iloprost had no effect on myometrial strips from control animals not in labor.

CONCLUSION: These findings indicate up-regulation of IP receptors which inhibit myometrial contractility and/or down-regulation of EP(1) receptors which stimulate myometrial contractility in the lower uterine segment during labor. A relative increase in inhibitory responses in the lower uterine segment during labor may enable this region to dilate to allow passage of the fetus.