Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC347
The effects of gestation and agonists on the ability of magnesium to reduce uterine contractility
A. McCullough1, H. Wood1, J. Prescott1, A. Heath1, K. Noble1, J. Neilson2, S. Wray1
1. Cellular and Molecular Physiology, University of Liverpool, Liverpool, United Kingdom. 2. Perinatal & Reproductive Medicine, University of Liverpool, Liverpool, United Kingdom.
Magnesium is able to inhibit smooth muscle contractility; an effect attributed to inhibition of L-type Ca channel entry, and as such is used as a uterine tocolytic. Although it is cheap and readily available, its efficacy has been seriously questioned. We have therefore examined two likely variables on its efficacy; stage of gestation and hormonal background, as little is known about how these may influence the myometrial response to increasing [Mg]. Myometrium was dissected from non-pregnant, day 14 and day 22 pregnant rats and from biopsies from women having term, elective Caesarean sections (with consent and ethical approval). Tissues were superfused with physiological saline, Ca 2 mM, pH 7.4, temperature 37 oC and tension measured. Magnesium sulphate was incrementally increased in this solution from 1.2 up to 15 mM and effects on contraction amplitude, frequency and area under the curve (auc) determined. In some experiments oxytocin (1nM, human, 0.5nM rat) or high-K (40mM) were used. Elevation of [Mg] produced a dose-dependent inhibition of uterine spontaneous activity. In non-pregnant and day 14 pregnant rats, force was abolished when Mg was raised to 2.0 mM Mg, n=5. Elevation of external Ca to 4-5mM restored contractions to control levels. In contrast, in term pregnant myometrium of rats and women, at 2.0mM Mg, force amplitude (control =100%) was reduced but not abolished : 60+10%, n=14, and 43+17% n=7, respectively. Similar reductions were found in the other parameters of contraction. Contractions were abolished at 2.6 mM in all preparations. Application of oxytocin significantly increased the amount of Mg required to affect contractions in term myometrium, such that 2mM was without effect and to abolish contractions 10- 14 mM were required. Similar preliminary results were obtained with high K stimulation. We conclude that (i) the myometrium irrespective of species, gestation and mechanism of stimulation is sensitive to Mg in a dose-dependent manner but (ii) changes associated with the transition to labour reduce its effectiveness. Thus, variations between women in progression to labour could explain why it is not a reliable tocolytic in vivo. Magnesium’s action appears to be via L-type Ca channel inhibition and measurements of intracellular Ca are on-going to test this further.
Where applicable, experiments conform with Society ethical requirements