Inhibitory Effect of Iloprost on the Contractility of Lower Uterine Segment Myometrium From Rhesus Monkey in Normal-Term and Androstenedione-Induced Preterm Labor

Abstract

Objective: Iloprost, a combined EP₁ 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 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 artey and vein catheres and uterine electromyogram leads. Experimental animals were infused with undrostenedione 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 suprefusion 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 myonetrial contractility and/or down-regulation of EP₁ 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.

Keywords

Labor myometrium prostaglandin receptors lower uterine segment nonhuman primate

Get full access to this article

View all access options for this article.

References

1. Mecenas CA , Giussani DA , Owiny JR , et al. Production of premature delivery in pregnant rhesus monkeys by androstenedione infusion. Nat Med 1996;2:443-448.

2. Sheldrick RLG , Coleman RA , Lumley P . Iloprost—a potent EP1 and IP-receptor agonist. Br J Pharmacol 1988;94:334P-334P.

3. Garcia-Villar R , Greem LR , Jenkins SL , Wentworth RA , Coleman RA , Nathanielz PW . Evidence for the presence of AH 13205-sensitive EP2-prostanoid receptors in pregnant baboon but not in the pregnant sheep myometrium near term. J Soc Gynecol Invest 1995;2:6-12.

4. MacDonald PC , Casey ML . The accumulation of prostaglandins (PG) in amniotic fluid is an aftereffect of labor and not indicative of a role for PGE2 or PGF2a in the initiation of human parturition. J Clin Endocrinol Metab 1993;76:1332-1339.

5. Romero R , Gonzalez R , Baumann P , et al. Topographic differences in amniotic fluid concentrations of prostanoids in women in spontaneous labor at term. Prostaglandis Leukot Essent Fatty Acids 1994;50:97-104.

6. Ou CW , Chen ZQ , Qi S , Lye SJ . Increased expression of the rat myometrial oxytocin receptor messenger ribonucleic acid during labor requires both mechnical and hormonal signals. Biol Resprod 1998;59:1055-1061.

7. Wu WX , Ma XH , Yoshizato T , Shinozuka N , Nathanielsz PW . Differential expression of myonetrial oxytocin receptor and prostaglandin H synthase 2, but not estrogen receptor α and heat shock protein messenger ribouncleic acid in the gravid horn and nongravid horn in sheep during betamethasone-induced labor. Endocrinology 1999;140:5712-5718.

8. Smith GCS , Baguma-Nibasheka M , Wu WX , Nathanielsz PW . Regional variations in contractile reponses to prostaglandins and prostanoid receptor messanger ribonucleic acid in pregnant baboon uterus. Am J Obstet Gynecol 1998;179:1545-1552.

9. Senior J , Marshall K , Sangha R , Baxter GS , Clayton JK , In vitro characterization of prostanoid EP-receptors in the non-pregnant human myometrium. Br J Pharmacol 1991;102:747-753.

10.

10. Senior J , Sangh R , Baxter GS , Marshall K , Clayton JK , In vitro characterization of prostanoid FP-, DP-, IP-and TP-receptors in the non-pregnant human myometrium. Br J Pharmacol 1992;107:215-221.

11.

11. Senior J , Marshall K , Sangha R , Clayton JK , In vitro characterization of prostanoid receptors on huma myometrium at term pregnancy. Br J Pharmacol 1993;108:501-506.