Preventive effect of ritodrine hydrochloride and/or urinary trypsin inhibitor against lipopolysaccharide-induced preterm delivery in mice

Background. The purpose of this study was to confirm the preventive effect of ritodrine hydrochloride (ritodrine) alone or ritodrine plus urinary trypsin inhibitor (UTI) in a mouse model of preterm delivery. Methods. On day 17 of pregnancy, female C3H/HeN mice impregnated by male B6D2F1 mice were given two intraperitoneal injections of lipopolysaccharide (LPS) (50 μg/kg) at a 3-hour interval, which induced a 100% incidence of preterm delivery within 25 hours of the second dose. Ritodrine (1, 3, or 10 mg/kg, po), UTI (25 × 104units/kg, ip), ritodrine (3 mg/kg, po) plus UTI (25X104units/kg, ip), distilled water (10 ml/kg, po), or distilled water (10 mg/kg, po) plus saline solution (10 ml/kg, ip) were administered to the pregnant animals 10 times at 1-hour intervals from 8:00 AM to 5:00 PM on day 18 of pregnancy. In addition, the preventive effect of ritodrine, UTI, or ritodrine plus UTI was examined on LPS-induced contraction of uterine muscle strips isolated from pregnant mice on day 17 of gestation. Results. The incidence of preterm delivery decreased significantly in a dose-dependent fashion with ritodrine treatment, and there was a significant and synergistic decrease after combined treatment with ritodrine plus UTI. The in vitro uterine contraction induced by LPS was significantly suppressed by both ritodrine and UTI. Conclusions. Combination therapy with ritodrine plus UTI may be helpful for preventing preterm delivery in humans without the cardiovascular side effects that often accompany treatment with ritodrine alone.