Thrombin-stimulated uterine contractions in the pregnant and nonpregnant rat

OBJECTIVE: Thrombin generated during the active clotting of blood appears t o be a potent uterotonic agonist; however, the mechanism underlying this ef fect on uterine smooth muscle is not well understood. We performed studies to confirm the uterotonic effects of thrombin and to determine whether pros taglandin production plays a role during the uterotonic effects of thrombin or clotting blood. METHODS: Uterine contraction studies were performed using adult nonpregnant and near-term pregnant rats. The in vitro isometric contraction studies us ed uterine strips pretreated with indomethacin or vehicle (ethanol), which were then stimulated with thrombin. For the lit vivo contraction studies, r ats were pretreated with intraperitoneal injections of indomethacin or vehi cle (ethanol) then stimulated by intraluminal injection of fresh rat blood or thrombin into the uterus. The contraction data were acquired using isome tric force tranducers. were computer digitized, normalized for spontaneous activity, and statistically analyzed. Prostaglandin (PG) F-2 alpha was meas ured using an enzyme-linked immunoassay. RESULTS: The in vitro contraction studies demonstrated that both thrombin m id actively clotting blood produce a significant increase in the frequency and intensity of uterine contractions. Thrombin stimulation was associated with a 54% increase in PGF(2 alpha) concentration in vitro; indomethacin (1 muM) pretreatment completely inhibited that increase in PGF(2 alpha) produ ction. Despite the suppression of PGF(2 alpha) production, pretreatment wit h indomethacin had iio inhibitory ft ct on thrombin-stimulated contractile activity. lit vivo contraction studies further confirmed that indomethacin (2 mg/kg) pretreatment had no effect on blood- or thrombin-stimulated contr actile activity. CONCLUSIONS: We confirmed that thrombin and thrombin produced by actively c lotting blood had a robust uterotonic effect in in the rat and that prostag landin production did not play a significant role in thrombin-stimulated co ntractions. Copyright (C) 2001 by the Society for Gynecologic Investigation .