Modification of the effect of nifedipine in the pregnant rat myometrium: The influence of progesterone and terbutaline

Aug 26, 2009Life sciences

How progesterone and terbutaline change nifedipine’s effect on pregnant rat uterine muscle

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Abstract

The relaxing effect of nifedipine on uterine contractions is most pronounced on day 22 of pregnancy.

Nifedipine exhibited its strongest relaxation effect during KCl-induced contractions at a concentration of 25 mM.
Progesterone pretreatment in vivo reduced the relaxing effect of nifedipine.
A synergistic effect was noted when nifedipine was combined with terbutaline, but the effectiveness varied based on the order of administration.
Administering terbutaline before nifedipine resulted in a lower maximal inhibitory effect of nifedipine.
The decreased inhibition caused by terbutaline was found to be influenced by the presence of calcium ions.

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AIMS: 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.

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

KEY FINDINGS: 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.

SIGNIFICANCE: 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.

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Modification of the effect of nifedipine in the pregnant rat myometrium: The influence of progesterone and terbutaline

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