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


METHODS
Experimental animal and human myometrial studies.


METHODS
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-E(2). 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 β(2)-mimetics, or abolished after progesterone pretreatment. Synergism was observed in the relaxing effects of nifedipine and terbutaline on the isolated human myometrium.


CONCLUSIONS
The action of nifedipine in delaying labor is impeded by progesterone. A combination of nifedipine and β(2)-agonists should be considered for the treatment or prevention of preterm birth.
Hajagos-Tóth
Judit
J
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.
Kormányos
Zsolt
Z
Falkay
George
G
Pál
Attila
A
Gáspár
Róbert
R
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology; D023421:Models, Animal; D009215:Myometrium / Q000187:drug effects; D009543:Nifedipine / Q000008:administration & dosage* / Q000494:pharmacology*; D010120:Oxytocics / Q000008:administration & dosage / Q000494:pharmacology; D011247:Pregnancy; D047928:Premature Birth / Q000517:prevention & control*; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068299:Salmeterol Xinafoate; D015145:Tocolysis / Q000379:methods; D015149:Tocolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D010120:Oxytocics; D015149:Tocolytic Agents; D015735:Mifepristone; D011374:Progesterone; D000068299:Salmeterol Xinafoate; D009543:Nifedipine; D000420:Albuterol