Endothelin-1 potentiates the in vitro contractile response of pregnant human myometrium to oxytocin

OBJECTIVE: This study was designed to test the hypothesis that endothelin-1 pretreatment of human myometrium at subcontractile doses in vitro will enhance the contractile response to oxytocin. STUDY DESIGN: In vitro contractile oxytocin dose-response curves were generated by use of myometrial strips collected from nonpregnant women (n = 7), pregnant patients at elective cesarean section (n = 7), and pateints in active labor (n = 7) in the presence or absence of 10−9 mol/L endothelin-1. Contractile responses were analyzed by on-line computer, and data were normalized to the maximum response to potassium. RESULTS: Pretreatment with endothelin-1 significantly increased the maximal contractile response of pregnant myometrium (p< 0.01 compared with control). In marked contrast myometrium from nonpregnant patients was unaffected by endothelin-1 pretreatment. Values for the two-point discrimination and Hill coefficient were not different among the treatment groups. CONCLUSION: Endothelin-1 potentiates the oxytocin response of myometrium from pregnant but not nonpregnant women. We speculate that a high circulating level of a uterotonin-like oxytocin may not be necessary to initiate labor. The synergistic interaction between different uterotonins may be sufficient.