Skip to main content
SpringerLink
Log in

Oxytocin Pretreatment Decreases Oxytocin-induced Myometrial Contractions in Pregnant Rats in a Concentration-dependent But Not Time-dependent Manner

  • Published:
Reproductive Sciences Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mitchell BF, Fang X, Wong S. Oxytocin: a paracrine hormone in the regulation of parturition? Rev Reprod. 1998;3: 113–122.

    Article  CAS  Google Scholar 

  2. Phaneuf S, Europe-Finner GN, Vamey M, MacKenzie IZ, Watson SP, Lopez Bemal A. Oxytocin-stimulated phosphoi-nositide hydrolysis in human myometrial cells: involvement of pertussis toxin-sensitive and -insensitive G-proteins. J Endocrinol. 1993;136:497–509.

    Article  CAS  Google Scholar 

  3. Robinson C, Schumann R, Zhang P, Young RC. Oxytocin-induced desensitization of the oxytocin receptor. Am J Obstet Gynecol. 2003;188:497–502.

    Article  CAS  Google Scholar 

  4. Phaneuf S, Asboth G, Carrasco MP, et al. Desensitization of oxytocin receptors in human myometrium. Hum Reprod Update. 1998;4:625–633.

    Article  CAS  Google Scholar 

  5. Phaneuf S, Rodriguez Linares B, TambyRaja RL, MacKenzie IZ, Lopez Bemal A. Loss of myometrial oxytocin receptors during oxytocin-induced and oxytocin-augmented labour. J Reprod Fertil. 2000;120:91–97.

    Article  CAS  Google Scholar 

  6. Phaneuf S, Asboth G, MacKenzie IZ, Melin P, Lopez Bernal A. Effect of oxytocin antagonists on the activation of human myometrium in vitro: atosiban prevents oxytocin-induced desensitization. Am J Obstet Gynecol. 1994;171:1627–1634.

    Article  CAS  Google Scholar 

  7. Adachi S, Oku M. The regulation of oxytocin receptor expression in human myometrial monolayer culture. J Smooth Muscle Res. 1995;31:175–187.

    Article  CAS  Google Scholar 

  8. Phaneuf S, Asboth G, Carrasco MP, et al. The desensitization of oxytocin receptors in human myometrial cells is accompanied by down-regulation of oxytocin receptor messenger KNA. J Endocrinol. 1997;154:7–18.

    Article  CAS  Google Scholar 

  9. Karsli B, Kayacan N, Kucukyavuz Z, Mimaroglu C. Effects of local anesthetics on pregnant uterine muscles. Pol J Pharmacol. 2003;55:51–56.

    CAS  PubMed  Google Scholar 

  10. Yoo KY, Lee J, Kim HS, Jeong SW. The effects of opioids on isolated human pregnant uterine muscles. Anesth Analg. 2001;92:1006–1009.

    Article  CAS  Google Scholar 

  11. Choi J, Hammer LW, Hester RL. Calcium-dependent synthesis of prostacyclin in ATP-stimulated venous endothelial cells. Hypertension. 2002;39:581–585.

    Article  CAS  Google Scholar 

  12. Li Z, Zhou L, Tang Hui-fang. Effects of levobupivacaine and bupivacaine on rat myometrium. J Zhejiang Univ Sci B. 2006;7:757–762.

    Article  CAS  Google Scholar 

  13. Bengtsson B, Chow EM, Marshall JM. Activity of circular muscle of rat uterus at different times in pregnancy. Am J Physiol. 1984;246:C216–C223.

    Article  CAS  Google Scholar 

  14. Meisheri KD, McNeill JH, Marshall JM. Effect of isoproterenol on the isolated pregnant rat myometrium. Eur J Pharmacol. 1979;60:1–6.

    Article  CAS  Google Scholar 

  15. Carvalho JC, Balki M, Kingdom J, Windrim R. Oxytocin requirements at elective cesarean delivery: a dose-finding study. Obstet Gynecol. 2004;104:1005–1010.

    Article  CAS  Google Scholar 

  16. Balki M, Ronayne M, Davies S, et al. Minimum oxytocin dose requirement after cesarean delivery for labor arrest. Obstet Gynecol. 2006;107:45–50.

    Article  CAS  Google Scholar 

  17. Kantas E, Cetin A, Kaya T, Cetin M. Effect of magnesium sulfate, isradipine, and ritodrine on contractions of myometrium: pregnant human and rat. Acta Obstet Gynecol Scand. 2002;81:825–830.

    Article  Google Scholar 

  18. Yildiz K, Dogru K, Dalgic H, et al. Inhibitory effects of des-flurane and sevoflurane on oxytocin-induced contractions of isolated pregnant human myometrium. Acta Anaesthesiol Scand. 2005;49:1355–1359.

    Article  CAS  Google Scholar 

  19. Fielitz CA, Gonzalez Panizza VH, Caldeyro-Barcia R. Effect of low concentrations of oxytocin on the uterine response to electrical stimulation. Acta Physiol Lat Am. 1960;10:201–204.

    CAS  PubMed  Google Scholar 

  20. Higuchi T, Todokoro Y, Honda K, Negoro H. Detailed analysis of blood oxytocin levels during suckling and parturition in the rat. J Endocrinol. 1986;110:251–256.

    Article  CAS  Google Scholar 

  21. Goodfellow CF, Hull MG, Swaab DF, Dogterom J, Buijs RM. Oxytocin deficiency at delivery with epidural analgesia. Br J Obstet Gynaecol. 1983;90:214–219.

    Article  CAS  Google Scholar 

  22. Seitchik J, Amico J, Robinson AG, Castillo M. Oxytocin augmentation of dysfunctional labor. IV. Oxytocin pharmacokinetics. Am J Obstet Gynecol. 1984;150:225–228.

    Article  CAS  Google Scholar 

  23. Garfield RE, Blennerhasssett MG, Miller SM. Control of myometrial contractility: role and regulation of gap junctions. Oxf Rev Reprod Biol. 1988;10:436–490.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesia and Pain Management Department of Obstetrics and Gynaecology Mount Sinai Hospital, 600 University Avenue, M5G 1X5, Ontario, Toronto, Canada

    Joyce K. R. S. Magalhaes MD, Jose C. A. Carvalho MD, PhD, John Kingdom MD, Yong Li MD & Mrinalini Balki MD

  2. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada

    Robert K. Parkes MSc

Authors
  1. Joyce K. R. S. Magalhaes MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jose C. A. Carvalho MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert K. Parkes MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John Kingdom MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yong Li MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mrinalini Balki MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mrinalini Balki MD.

Additional information

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.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719108329954

Key words

Search

Navigation