Combined uterorelaxant effect of magnesium sulfate and terbutaline: Studies on late pregnant rat uteri in vitro and in vivo

Abstract Introduction Preterm delivery and its complications are among the biggest challenges and health risks in obstetrical practice. Several tocolytic agents are used in clinical practice, although the efficacy and side effect profiles of these drugs are not satisfying. The aim of this study was...

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Main Authors: Tamara Barna, Kalman F. Szucs, Annamaria Schaffer, Mohsen Mirdamadi, Judit Hajagos‐Toth, Robert Gaspar
Format: Article
Language:English
Published: Wiley 2023-04-01
Series:Acta Obstetricia et Gynecologica Scandinavica
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Online Access:https://doi.org/10.1111/aogs.14532
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author Tamara Barna
Kalman F. Szucs
Annamaria Schaffer
Mohsen Mirdamadi
Judit Hajagos‐Toth
Robert Gaspar
author_facet Tamara Barna
Kalman F. Szucs
Annamaria Schaffer
Mohsen Mirdamadi
Judit Hajagos‐Toth
Robert Gaspar
author_sort Tamara Barna
collection DOAJ
description Abstract Introduction Preterm delivery and its complications are among the biggest challenges and health risks in obstetrical practice. Several tocolytic agents are used in clinical practice, although the efficacy and side effect profiles of these drugs are not satisfying. The aim of this study was to investigate the uterus relaxant effect of the coadministration of β2‐mimetic terbutaline and magnesium sulfate (MgSO4) in an isolated organ bath and to perform in vivo smooth muscle electromyographic (SMEMG) studies in pregnant rats. In addition, we also investigated whether the tachycardia‐inducing effect of terbutaline can be reduced by the presence of magnesium, due to the opposite heart rate modifying effects of the two agents. Material and methods In the isolated organ bath studies, rhythmic contractions of 22‐day‐ pregnant Sprague–Dawley rats were stimulated with KCl, and cumulative dose–response curves were constructed in the presence of MgSO4 or terbutaline. The uterus‐relaxing effects of terbutaline were also investigated in the presence of MgSO4 in both normal buffer and Ca2+‐poor buffer. The in vivo SMEMG studies were carried out under anesthesia with the subcutaneous implantation of an electrode pair. The animals were treated with MgSO4 or terbutaline alone or in combination in a cumulative bolus injection. The implanted electrode pair also detected the heart rate. Results Both MgSO4 and terbutaline reduced uterine contractions in vitro and in vivo, furthermore, the administration of a small dose of MgSO4 significantly enhanced the relaxant effect of terbutaline, especially in the lower range. However, in Ca2+‐poor environment, MgSO4 was not able to increase the effect of terbutaline, indicating the role of MgSO4 as a Ca2+ channel blocker. In the cardiovascular studies, MgSO4 significantly decreased the tachycardia‐inducing effect of terbutaline in late pregnant rats. Conclusions The combined application of MgSO4 and terbutaline may have clinical significance in tocolysis, which must be confirmed in clinical trials. Furthermore, MgSO4 could substantially reduce the tachycardia‐inducing side effect of terbutaline.
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spelling doaj-art-75fb39d0ddb2490b83d5f0f06bfdd9212025-08-20T03:22:18ZengWileyActa Obstetricia et Gynecologica Scandinavica0001-63491600-04122023-04-01102445746410.1111/aogs.14532Combined uterorelaxant effect of magnesium sulfate and terbutaline: Studies on late pregnant rat uteri in vitro and in vivoTamara Barna0Kalman F. Szucs1Annamaria Schaffer2Mohsen Mirdamadi3Judit Hajagos‐Toth4Robert Gaspar5Department of Pharmacology and Pharmacotherapy Albert Szent‐Györgyi Medical School University of Szeged Szeged HungaryDepartment of Pharmacology and Pharmacotherapy Albert Szent‐Györgyi Medical School University of Szeged Szeged HungaryDepartment of Pharmacology and Pharmacotherapy Albert Szent‐Györgyi Medical School University of Szeged Szeged HungaryDepartment of Pharmacology and Pharmacotherapy Albert Szent‐Györgyi Medical School University of Szeged Szeged HungaryDepartment of Pharmacology and Pharmacotherapy Albert Szent‐Györgyi Medical School University of Szeged Szeged HungaryDepartment of Pharmacology and Pharmacotherapy Albert Szent‐Györgyi Medical School University of Szeged Szeged HungaryAbstract Introduction Preterm delivery and its complications are among the biggest challenges and health risks in obstetrical practice. Several tocolytic agents are used in clinical practice, although the efficacy and side effect profiles of these drugs are not satisfying. The aim of this study was to investigate the uterus relaxant effect of the coadministration of β2‐mimetic terbutaline and magnesium sulfate (MgSO4) in an isolated organ bath and to perform in vivo smooth muscle electromyographic (SMEMG) studies in pregnant rats. In addition, we also investigated whether the tachycardia‐inducing effect of terbutaline can be reduced by the presence of magnesium, due to the opposite heart rate modifying effects of the two agents. Material and methods In the isolated organ bath studies, rhythmic contractions of 22‐day‐ pregnant Sprague–Dawley rats were stimulated with KCl, and cumulative dose–response curves were constructed in the presence of MgSO4 or terbutaline. The uterus‐relaxing effects of terbutaline were also investigated in the presence of MgSO4 in both normal buffer and Ca2+‐poor buffer. The in vivo SMEMG studies were carried out under anesthesia with the subcutaneous implantation of an electrode pair. The animals were treated with MgSO4 or terbutaline alone or in combination in a cumulative bolus injection. The implanted electrode pair also detected the heart rate. Results Both MgSO4 and terbutaline reduced uterine contractions in vitro and in vivo, furthermore, the administration of a small dose of MgSO4 significantly enhanced the relaxant effect of terbutaline, especially in the lower range. However, in Ca2+‐poor environment, MgSO4 was not able to increase the effect of terbutaline, indicating the role of MgSO4 as a Ca2+ channel blocker. In the cardiovascular studies, MgSO4 significantly decreased the tachycardia‐inducing effect of terbutaline in late pregnant rats. Conclusions The combined application of MgSO4 and terbutaline may have clinical significance in tocolysis, which must be confirmed in clinical trials. Furthermore, MgSO4 could substantially reduce the tachycardia‐inducing side effect of terbutaline.https://doi.org/10.1111/aogs.14532magnesium sulfatepregnancytocolysisuterine contractilityβ2‐adrenoreceptor agonists
spellingShingle Tamara Barna
Kalman F. Szucs
Annamaria Schaffer
Mohsen Mirdamadi
Judit Hajagos‐Toth
Robert Gaspar
Combined uterorelaxant effect of magnesium sulfate and terbutaline: Studies on late pregnant rat uteri in vitro and in vivo
Acta Obstetricia et Gynecologica Scandinavica
magnesium sulfate
pregnancy
tocolysis
uterine contractility
β2‐adrenoreceptor agonists
title Combined uterorelaxant effect of magnesium sulfate and terbutaline: Studies on late pregnant rat uteri in vitro and in vivo
title_full Combined uterorelaxant effect of magnesium sulfate and terbutaline: Studies on late pregnant rat uteri in vitro and in vivo
title_fullStr Combined uterorelaxant effect of magnesium sulfate and terbutaline: Studies on late pregnant rat uteri in vitro and in vivo
title_full_unstemmed Combined uterorelaxant effect of magnesium sulfate and terbutaline: Studies on late pregnant rat uteri in vitro and in vivo
title_short Combined uterorelaxant effect of magnesium sulfate and terbutaline: Studies on late pregnant rat uteri in vitro and in vivo
title_sort combined uterorelaxant effect of magnesium sulfate and terbutaline studies on late pregnant rat uteri in vitro and in vivo
topic magnesium sulfate
pregnancy
tocolysis
uterine contractility
β2‐adrenoreceptor agonists
url https://doi.org/10.1111/aogs.14532
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