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Potentiation of the uterus-relaxing effects of β-adrenergic agonists with nifedipine: studies on rats and the human myometrium

Authors


Róbert Gáspár, Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, P.O. Box 121, Szeged H-6701, Hungary. gaspar@pharm.u-szeged.hu

Abstract

Objective. We investigated how progesterone and salmeterol modify the effect of nifedipine in an in vivo preterm birth model in rats, and how terbutaline and nifedipine modify the contractions of the isolated human myometrium. Design. Experimental animal and human myometrial studies. Sample. Twenty-four female Sprague–Dawley rats and 13 human uterine tissues sampled from cesarean section. Methods. Preterm birth was induced in Sprague–Dawley rats with a combination of mifepristone and prostaglandin-E2. The animals were treated with nifedipine or its combination with salmeterol and progesterone. Additionally, isolated human myometrial strips from cesarean sections were stimulated with oxytocin, and the inhibitory effects of nifedipine and terbutaline were studied. Results. Nifedipine delayed the preterm delivery in the rats, but its effect was tripled by the addition of β2-mimetics, or abolished after progesterone pretreatment. Synergism was observed in the relaxing effects of nifedipine and terbutaline on the isolated human myometrium. Conclusion. The action of nifedipine in delaying labor is impeded by progesterone. A combination of nifedipine and β2-agonists should be considered for the treatment or prevention of preterm birth.

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