Antenatal montelukast treatment reduces uterine activity associated with inflammation in a pregnant rat model.

OBJECTIVE: The potency of acute montelukast treatment, a leukotriene receptor antagonist, has been demonstrated as tocolytic on in vitro myometrial contractility. This study assessed the ability of a 48h montelukast treatment to modify in vitro contractions under inflammatory conditions in a pregnant rat model.

STUDY DESIGN: Pregnant Sprague-Dawley rats were injected intraperitoneally (gestational days 20-22) with lipopolysaccharides (LPS) 200μg/kg (4 treatments at 12h intervals) alone or combined with montelukast 10mg/kg/day or a saline solution for a 48h period. Uterine rings (n=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 in vitro experiments, the area under the curve, the amplitude and the duration of phasic contractions were significantly reduced following 48h of LPS+montelukast treatment comparatively to the LPS group. Moreover, in this same group, oxytocin (10(-9)-10(-7)M) largely decreased uterine sensitivity (p=0.04). Following LPS and montelukast treatment, the tocolytic effectiveness of nifedipine (10(-9)-10(-7)M) was increased (p<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.