ABSTRACT
UNLABELLED: Tocolysis is one of the greatest challenges in obstetrical practice. It is known that the calcium channel antagonists abolish the intracellular calcium ion transients and myometrial contraction. However there is a growing interest in experimental studies to use different tocolytic combination. The aims of the study were to investigate the effects of nifedipine on potassium chloride (KCl)-evoked rat uterine contractions on the last day of pregnancy (22) in vitro, and the alterations in the effects of nifedipine on combination with BK(Ca-channel blockers paxillin and tetraethyl ammonium chloride in late pregnancy in vitro. An other aim was to investigate the modification of the effect of nifedipine by terbutaline on the contraction of isolated rat and human myometrium. For human myometrial rings rhythmic contractions were evoked with oxytocin in an isolated organ bath. KCl-stimulated uterine contractions were inhibited concentration-dependently by nifedipine. In the presence of the potassium channel blockers, the action of nifedipine was not modified. Synergism was observed in the uterus-relaxing effect of nifedipine and terbutaline, though the extent of potentiation depended on the sequence of the 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 Ca2+ channel activating effect of terbutaline. However, in the isolated organ bath studies the BK(Ca) channel had no effect on the uterus relaxing effect of nifedipine in spite of literature. CONCLUSION: It is concluded that the combination of nifedipine and beta2-agonists should be considered for clinical use. However, the administration of terbutaline can not precede the administration of nifedipine.
