Uterine contractile responses to endothelin-1 and endothelin receptors are elevated during labor

The purpose of this study was to determine whether the contractile responsiveness of the rat uterus to endothelin (ET)-1 and myometrial ET-1 receptors is elevated during labor. Uterine contractile responses to ET-1 were measured in isolated uterine strips obtained from rats on Day 18 of gestation, during spontaneous labor at term, and on Days 1 and 2 postpartum. The mean force (millinewtons) generated by cumulative addition of ET-1 (10(-10)-10(-6) M) was measured in vitro. Cumulative dose-response curves were created based upon the contractile activity vs. log doses of ET-1. The values of the estimated pD2, Emax, and slope of the dose-response curves were significantly (p < 0.05) higher in tissues taken during delivery than in tissues from animals on Day 18 of gestation or Days 1 and 2 postpartum. Myometrial ET-1 receptors were also measured during pregnancy and labor. Scatchard analysis of the ET-1 binding to myometrial membranes revealed that receptor levels were significantly (p < 0.05) elevated in delivering animals, without changes in their affinity. Our study shows that the uterus is more sensitive and responsive to the contractile effects of ET-1 during labor, at term, when the receptor density is increased. The change in ET-1 responsiveness at term may play a role in the initiation and/or progression of labor.