Abstract
Recent biomolecular studies have shown that continuous exposure of human myometrial cells to oxytocin results in a significant loss of responsiveness to subsequent oxytocin stimulation, perhaps because of desen-sitization of the oxytocin receptors. However, it is unclear whether this phenomenon results in a reduction of the contractile activity of the uterine muscle in humans or animals. The objective of our study was to investigate the in vitro response of the uterine muscle of pregnant rats to oxytocin, following preexposure to varying concentrations of oxytocin, for varying durations. Longitudinal myometrial strips were isolated from 16 pregnant Wistar rats at 19 to 21 days of gestation and preexposed to oxytocin 10 or 10–8 mol/L (experimental groups) or physiological salt solution (control groups) for 1- or 4-hour period. All muscle strips were then subjected to a dose-response study with oxytocin 10 to 10 mol/L. The area under the curve, frequency, and amplitude of contractions were recorded and compared between the groups. The area under the curve, frequency, and amplitude of the oxytocin-induced contractions were all significantly suppressed in the groups preexposed to oxytocin 10 mol/L compared to either the control groups (P < .0001) or the groups preexposed to oxytocin 10 mol/L (P < .0001). There was no difference in the oxytocin-induced myometrial contractions between the groups preexposed to oxytocin for either the 1- or 4-hour periods. The inhibition of the oxytocin-induced contractile response of pregnant rat myometrium is observed as early as 1 hour of preexposure to oxytocin and is dependent on the preexposed oxytocin concentration and not on the duration of its exposure.
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This study was supported by funding from Dean’s Fund, University of Toronto; Department of Obstetrics & Gynaecology, Mount Sinai Hospital; and Department of Anesthesia, University Health Network-Mount Sinai Hospital (UHN-MSH), University of Toronto.
This paper won the award for “Best paper in Obstetric Anesthesia” at the Canadian Anesthesiology’s Society Meeting, Halifax, Nova Scotia, June 13–17, 2008. It was also presented as oral presentation in the best paper competition at the 40th Annual Meeting of the Society for Obstetric Anesthesia and Perinatology, Chicago, Illinois, April 30-May 4, 2008. We would like to thank Dr Stephen Lye, Associate Director, Research, and Dr Lee Adamson, Senior Investigator, Samuel Lunenfeld Research Institute, for providing us with the lab space as well as for their guidance and support while we were setting up the lab. We would like to acknowledge Dr Marco Magalhaes for his generous help with the equipment assembly and technical support. We are grateful to Dr Venu Jain, Dr Steffen-Sebastian Bolz, and Dr Jaques Belik from the University of Toronto for their continual guidance during the conduct of the experiments.
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Magalhaes, J.K.R.S., Carvalho, J.C.A., Parkes, R.K. et al. Oxytocin Pretreatment Decreases Oxytocin-induced Myometrial Contractions in Pregnant Rats in a Concentration-dependent But Not Time-dependent Manner. Reprod. Sci. 16, 501–508 (2009). https://doi.org/10.1177/1933719108329954
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DOI: https://doi.org/10.1177/1933719108329954