GESTATIONAL CHANGES IN OXYTOCIN-INDUCED AND ENDOTHELIN-1-INDUCED CONTRACTILITY OF PREGNANT RAT MYOMETRIUM

The mechanical effects of KCl, oxytocin and endothelin-1 on pregnant rat myometrium were examined using intact strips and beta-escin-treated skinned strips. Myometrial tissues from delivering rats were more sensitive to 10.7 mM K+ compared to mid and late gestation. Maximum contractions induced by K+ were obtained at concentrations of 118 mM at mid and late gestation and during delivery. The maximum amplitude of contractions induced by oxytocin and endothelin-l compared to the 118 mM Kc-induced contraction increased during the progress of gestation. Maximum contractions induced by oxytocin and endothelin-l were greater than those induced by 118 mM KC at delivery, and maximum contractions by oxytocin were larger than those by endothelin-l during delivery. In 10 mu M nifedipine and Ca2+-free (containing 2 mM EGTA) solutions, 118 mM K+ contractions were completely abolished; however, both oxytocin and endothelin-l produced contractions. In Ca2+-free solutions, contractions by oxytocin were larger than those by endothelin-l. In skinned myometrial strips, guanosine 5'-O-thiotriphosphate (GTP, 1 mu M-1 mM), guanosine 5'-O-(gamma-thiotriphosphate) (GTP gamma S, 0.1-100 mu M) and oxytocin (1 nM-0.1 mu M) with 10 mu M GTP, but not endothelin-l with 10 mu M GTP increased Ca2+ sensitivity of contractile force. These results suggests that (1) the membrane permeability for Ca2+ and the number of receptors of oxytocin and endothelin-1 increase during the progress of gestation, (2) both oxytocin and endothelin-l produce contractions by activation of voltage-dependent Ca2+ channels and Ca2+ release from internal storage sites, (3) oxytocin, but not endothelin-l, coupled to receptors increases Ca2+ sensitivity to contractile proteins.