Effect of endothelin-1 on spontaneous contractions and effects of nimodipine and isradipine on endothelin-1-induced contractions in myometrial strips isolated from normal pregnant and preeclamptic women

To examine the effect of endothelin-1 (ET-1) on spontaneous contractile activity and the effects of nimodipine and isradipine on ET-1-induced contractile responses in myometrial strips isolated from normal pregnant and preeclamptic women. . Isolated myometrial strips were obtained from seven normal pregnant and seven preeclamptic women undergoing elective cesarean section and the strips were mounted in organ baths for recording of isometric tension. The effect of increasing concentration of ET-1 on spontaneous contractions and effects of increasing concentration of nimodipine and isradipine on ET-1-induced contractions were recorded. ET-1 dose-dependently (10(-11)-10(-8) M) increased the amplitude and frequency of spontaneous contractions in all myometrial strips obtained from normal pregnant and preeclamptic women. The increase in the amplitude of contractions in preeclamptic strips was significantly higher than that of normal strips. The increase in amplitude of contractions in normal and preeclamptic strips reached statistical significance beginning from the concentrations of 10(-9) M and 10(-11) M, respectively. ET-1 (10(-8) M) also increased the basal tone of all myometrial strips isolated from normal pregnant and preeclamptic women. When ET-1 (10(-8) M)-contracted myoinetrial strips were exposed to increasing concentrations of nimodipine (10(-6)-3x10(-5)M) and isradipine (10(-5)-3x10(-4) M), nimodipine and isradipine dose-dependently decreased the amplitude and frequency of contractions. The increase in contractile response with ET-1 was significantly higher in myometrial strips isolated from preeclamptic women compared to those of myometrial strips isolated from normal pregnant women. These increases in contractile response are at least in part mediated by dihydropyridine-sensitive calcium channels, since they were significantly reduced in the presence of increasing concentrations of nimodipine and isradipine.