The study was undertaken to investigate the influence of
lipopolysaccharide (LPS) on the uterine contraction inhibitory effects of
tocolytic agents such as
ritodrine,
magnesium, and
diethylamine/
nitric oxide (
DEA/NO), and on
prostaglandin (PG) E2 and
nitric oxide (NO) metabolite (NOx) production in pregnant mice at midgestation. Pregnant C57BL mice on day 14 of gestation were sacrificed 6 hours after
intraperitoneal injection of LPS (400 mug/kg) or vehicle. Uterine rings were equilibrated in
Krebs-Henseleit solution (37 degrees C) bubbled with 20% O (2) and 5% CO (2) (pH ~7.4) for sampling and isometric tension recording. The concentration levels of
PGE2 and NOx in the
solution were determined. Changes of spontaneous contractile activity in response to cumulative concentrations of
ritodrine,
magnesium, and the NO donor,
DEA/NO, from the baseline were determined. Integral contractile activity over 10 minutes at each concentration was calculated and expressed as percentage change from basal activity. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by the Dunnett test (significance: P < 0.05). LPS treatment significantly increased the production levels of
PGE2 and NOx (from 66.8 +/- 6.7 pg/g tissue to 147.0 +/- 29.0, from 51.0 +/- 5.4 pmol/2 muL/g tissue to 98.0 +/- 16.2, respectively), P < 0.05).
Ritodrine,
magnesium, and
DEA/NO inhibited spontaneous contractions concentration dependently in uterine rings from both LPS-treated and -untreated animals. Treatment with LPS significantly attenuated the maximal inhibition induced by
DEA/NO in uterine rings from pregnant mice. LPS significantly suppressed the uterine contraction inhibitory effects of
ritodrine at 10 (-8) M concentrations and of
magnesium at 4.2 mmol concentration ( P < 0.05). We concluded that the effects of
ritodrine and
magnesium may be reduced under inflammatory conditions because LPS increases the production levels of
PGE2 and NOx, which cause increased spontaneous contractions of the uterine myometrium. Therefore, when uterine contractions are not controlled by
tocolytics in pregnant patients with
preterm labor associated with
inflammation,
labor induction or pregnancy termination may become significant options in clinical practice.