Modification of the effect of nifedipine in the pregnant rat myometrium: the influence of progesterone and terbutaline.
OBJECTIVE
The aims of the study were to investigate the effects of nifedipine on potassium chloride (KCl)-evoked rat uterine contractions on different days of pregnancy in vitro, and the alterations in the effects of nifedipine on combination with terbutaline or progesterone.


METHODS
In rat myometrial rings taken on different days of pregnancy, rhythmic contractions were evoked with KCl in an isolated organ bath.


RESULTS
The relaxing effect of nifedipine was most expressed in the 25 mM KCl-induced uterine contractions, reaching the maximum on the last day of pregnancy (day 22). This effect was decreased by progesterone pretreatment in vivo. Synergism was observed in the uterus-relaxing effect of nifedipine+terbutaline, though the extent of potentiation depended on the sequence of administration of the two compounds. When terbutaline was added first in a single dose, the maximal inhibitory effect of nifedipine was lower. This decrease in the inhibition was suspended by a Ca(2+)-poor buffer, indicating the role of Ca(2+) channel activating effect of terbutaline.


CONCLUSIONS
It is concluded that the uterus-relaxing effect of nifedipine is weakened by progesterone and may be enhanced by low concentrations of beta-mimetics. However, the administration of terbutaline cannot precede the administration of nifedipine.
Hajagos-Tóth
Judit
J
Department of Pharmacodynamics and Biopharmacy, University of Szeged, H-6701, Hungary. judittoth@pharm.u-szeged.hu
Falkay
George
G
Gáspár
Róbert
R
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005865:Gestational Age; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects*; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D013726:Terbutaline / Q000008:administration & dosage / Q000494:pharmacology*; D015149:Tocolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
D015220:Calcium Channels; D018343:Receptors, Adrenergic, beta-2; D015149:Tocolytic Agents; D011374:Progesterone; D011189:Potassium Chloride; D009543:Nifedipine; D013726:Terbutaline