The potency of acute
montelukast treat
ment, a leukotriene receptor antagonist, has been de
monstrated as tocolytic on
m>in vitrom>
myo
metrial contractility. This study assessed the ability of a 48 h
montelukast treat
ment to
modify
m>in vitrom> contractions under infla
mmatory conditions in a pregnant rat
model.
Study design
Pregnant Sprague-Dawley rats were injected intraperitoneally (gestational days 20–22) with lipopolysaccharides (LPS) 200 μg/kg (4 treatments at 12 h intervals) alone or combined with montelukast 10 mg/kg/day or a saline solution for a 48 h period. Uterine rings (m>nm> = 72) were obtained by median laparotomy at day 22. Spontaneous contractile activities were compared using pharmacological compounds (oxytocin, nifedipine) along with assessment of contractile parameters. Myometrial subcellular fractions were also analyzed by Western blot to quantify oxytocin, cysteinyl leukotriene receptors and inflammation markers.
Results
In m>in vitrom> experiments, the area under the curve, the amplitude and the duration of phasic contractions were significantly reduced following 48 h of LPS + montelukast treatment comparatively to the LPS group. Moreover, in this same group, oxytocin (10−9–10−7 M) largely decreased uterine sensitivity (m>pm> = 0.04). Following LPS and montelukast treatment, the tocolytic effectiveness of nifedipine (10−9–10−7 M) was increased (m>pm> < 0.01). Western blot analysis confirmed the presence of type 1 CysLT receptors in all treated groups. Hence, montelukast treatment restored TNF-α and COX-2 basal levels.
Conclusion
Our results strongly suggest that montelukast treatment could facilitate a relative uterine quiescence by decreasing its sensitivity to uterotonic agent or by increasing tocolytic efficiency under proinflammatory conditions.