Skip to main content
SpringerLink
Log in

Oxytocin Pretreatment of Pregnant Rat Myometrium Reduces the Efficacy of Oxytocin but Not of Ergonovine Maleate or Prostaglandin F2α

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Oxytocin receptors (OTRs) in both human and rat myometrial cells are desensitized by exposure to oxytocin, thereby reducing the ability of the cells to respond to the subsequent administration of oxytocin. However, it is unclear if this desensitization phenomenon is confined to oxytocin, or extends to other uterotonic agents such as ergonovine or prostaglandin F2α (PGF2α). We compared the in vitro contractile responses of myometrial samples from pregnant Wistar rats at 20 to 22 days of gestation. Longitudinal myometrial strips isolated from each animal were pretreated with either oxytocin 10−8 mol/L (experimental groups) or physiological salt solution (control groups) for 1 hour in organ bath chambers, and then subjected to a dose-response study with oxytocin (n = 28), ergonovine (n = 16), or PGF2α (n = 16), with cumulative increases in the organ bath concentrations from 10−10 to 10−5 mol/L. The amplitude and frequency of the contractions during the dose-response period were analyzed using mixed linear modeling and compared between the groups. Oxytocin pretreatment significantly suppressed the mean amplitude of the myometrial contractions as compared to the controls when the strips were further subjected to oxytocin (1.02 vs 1.74 g; P < .0001), but not with further exposure to ergonovine (0.77 vs. 0.58 g; P = .11) or PGF2α (0.83 vs 0.94 g; P = .4). However, oxytocin produced superior contractions in the control and oxytocin-pretreated myometrium compared to either ergonovine or PGF2α. Our study shows that the uterotonic effects of ergonovine and PGF2α are not affected by the phenomenon of oxytocin desensitization in pregnant rat myometrium. However, oxytocin, despite the phenomenon of desensitization, provides superior uterine contractions when compared to ergonovine or PGF2α.

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. Joseph KS, Rouleau J, Kramer MS, Young DC, Liston RM, Baskett TF, for the Maternal Health Study Group of the Canadian Perinatal Surveillance System. Investigation of an increase in postpartum haemorrhage in Canada. BJOG. 2007;114(6):751–759.

    Article  CAS  Google Scholar 

  2. Brace V, Penney G, Hall M. Quantifying severe maternal morbidity: a Scottish population study. BJOG. 2004;111(5): 481–484.

    Article  Google Scholar 

  3. Maughan KL, Heim SW, Galazka SS. Preventing postpartum haemorrhage: managing the third stage of labour. Am Fam Physician. 2006;73(6):1025–1028.

    PubMed  Google Scholar 

  4. Cotter A, Ness A, Tolosa J. Prophylactic oxytocin for the third stage of labour. Cochrane Database Syst Rev. 2001;(4): CD001808.

    Google Scholar 

  5. Liabsuetrakul T, Choobun T, Peeyananjarassri K, Islam QM. Prophylactic use of ergot alkaloids in the third stage of labour. Cochrane Database of Syst. Rev. 2007;(2):CD005456.

    Google Scholar 

  6. Gülmezoglu AM, Forna F, Villar J, Hofmeyr GJ. Prostaglandins for preventing postpartum haemorrhage. Cochrane Database Syst Rev. 2007;(3):CD000494.

    Google Scholar 

  7. Robinson C, Schumann R, Zhang P, Young RC. Oxytocin-induced desensitization of the oxytocin receptor. Am J Obstet Gynecol. 2003;188(2):497–502.

    Article  CAS  Google Scholar 

  8. Phaneuf S, Asboth G, Carrasco MP, et al. Desensitization of oxytocin receptors in human myometrium. Hum Reprod Update. 1998;4(5):625–633.

    Article  CAS  Google Scholar 

  9. Phaneuf S, Rodriguez Linares B, TambyRaja RL, MacKenzie IZ, Lopez Bernal A. Loss of myometrial oxytocin receptors during oxytocin-induced and oxytocin-augmented labour. J Reprod Fertil. 2000;120(1):91–97.

    Article  CAS  Google Scholar 

  10. 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 RNA. J Endocrinol. 1997;154(1):7–18.

    Article  CAS  Google Scholar 

  11. Magalhaes J, Carvalho JCA, Parkes R, Kingdom J, Li Y, Balki M. Oxytocin pretreatment decreases oxytocin-induced myometrial contractions in pregnant rats in a concentration but not time-dependent manner. Reproductive Sciences. 2009; 16(5):501–508.

    Article  CAS  Google Scholar 

  12. Karsli B, Kayacan N, Kucukyavuz Z, Mimaroglu C. Effects of local anesthetics on pregnant uterine muscles. Pol J Pharmacol. 2003;55(1):51–56.

    CAS  Google Scholar 

  13. Yoo KY, Lee J, Kim HS, Jeong SW. The effects of opioids on isolated human pregnant uterine muscles. Anesth Analg. 2001; 92(4):1006–1009.

    Article  CAS  Google Scholar 

  14. Choi J, Hammer LW, Hester RL. Calcium-dependent synthesis of prostacyclin in ATP-stimulated venous endothelial cells. Hypertension. 2002;39(2 pt 2):581–585.

    Article  CAS  Google Scholar 

  15. Li Z, Zhou L, Tang Hui-fang. Effects of levobupivacaine and bupivacaine on rat myometrium. J Zhejiang Univ Sci B. 2006; 7(9):757–762.

    Article  CAS  Google Scholar 

  16. Bengtsson B, Chow EM, Marshall JM. Activity of circular muscle of rat uterus at different times in pregnancy. Am J Physiol. 1984;246(3 pt 1):C216–C223.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  18. Schuurmans N, MacKinnon C, Lane C, Etches D. Prevention and management of postpartum haemorrhage. J Soc Obstet Gynaecol Can. 2000;22(4):271–281.

    Google Scholar 

  19. ACOG Educational Bulletin. Postpartum Haemorrhage. Number 243, January 1998 (replaces No. 143, July 1990). American College of Obstetricians and Gynecologists. Int J Gynecol Obstet. 1998;61(1):79–86.

    Article  Google Scholar 

  20. Joint Formulary Committee. Obstetrics, gynaecology, and urinary-tract disorders. In: British National Formulary. 54th ed. London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2007:413–4116.

    Google Scholar 

  21. Gimpl G, Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiol Rev. 2001;81(2):629–683.

    Article  CAS  Google Scholar 

  22. de Groot AN, van Dongen PW, Vree TB, Hekster YA, van Roosmalen J. Ergot alkaloids. Current status and review of clinical pharmacology and therapeutic use compared with other oxytocics in obstetrics and gynaecology. Drugs. 1998; 56(4):523–535.

    Article  Google Scholar 

  23. Carboprost Tromethamine. http://www.mdconsult.com/das/pharm/body/111891555–5/777661948/full/1232. Accessed November 28, 2008.

  24. 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(9):825–830.

    Article  Google Scholar 

  25. Yildiz K, Dogru K, Dalgic H, et al. Inhibitory effects of desflurane and sevoflurane on oxytocin-induced contractions of isolated pregnant human myometrium. Acta Anaesthesiol Scand. 2005;49(9):1355–1359.

    Article  CAS  Google Scholar 

  26. Carvalho JC, Balki M, Kingdom J, Windrim R. Oxytocin requirements at elective cesarean delivery: a dose-finding study. Obstet Gynecol. 2004;104(5 pt 1):1005–1010.

    Article  CAS  Google Scholar 

  27. Balki M, Ronayne M, Davies S, Fallah S, Kingdom J, Windrim R, Carvalho JC. Minimum oxytocin dose requirement after cesarean delivery for labor arrest. Obstet Gynecol. 2006;107(1):45–50.

    Article  CAS  Google Scholar 

  28. Feldman R, Weller A, Zagoory-Sharon O, Levine A. Evidence for a neuroendocrinological foundation of human affiliation: plasma oxytocin levels across pregnancy and the postpartum period predict mother-infant bonding. Psychol Sci. 2007;18(11):965–970.

    Article  Google Scholar 

  29. Seitchik J, Amico J, Robinson AG, Castillo M. Oxytocin augmentation of dysfunctional labor. IV. Oxytocin pharmacokinetics. Am J Obstet Gynecol. 1984;150(3):225–228.

    Article  CAS  Google Scholar 

  30. Kuwabara Y, Takeda S, Mizuno M, Sakamoto S. Oxytocin levels in maternal and fetal plasma, amniotic fluid, and neonatal plasma and urine. Arch Gynecol Obstet. 1987;241(1): 13–23.

    Article  CAS  Google Scholar 

  31. 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  Google Scholar 

  32. Higuchi T, Todokoro Y, Honda K, Negoro H. Detailed analysis of blood oxytocin levels during suckling and parturition in the rat. J Endocrinology. 1986;110(2):251–256.

    Article  CAS  Google Scholar 

  33. Methylergonovine maleate. Mosby drug consult 2005, Mosby Inc. http://home.mdconsult.com/das/drug/body/3900545651/1/1789.html. Accessed November 20, 2007.

  34. Bygdeman M. Pharmacokinetics of prostaglandins. Best Pract Res Clin Obstet Gynaecol. 2003;17(5):707–716.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesia and Pain Management, Mount Sinai Hospital, University of Toronto, Room 1514, 600 University Avenue, M5G 1X5, Toronto, Ontario, Canada

    Mrinalini Balki MD, Alexandra L. Cristian BSc & Jose C. A. Carvalho MD, PhD

  2. Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Canada

    John Kingdom MD & Jose C. A. Carvalho MD, PhD

Authors
  1. Mrinalini Balki MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexandra L. Cristian BSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John Kingdom MD
    View author publications

    You can also search for this author in PubMed Google Scholar

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

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mrinalini Balki MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Balki, M., Cristian, A.L., Kingdom, J. et al. Oxytocin Pretreatment of Pregnant Rat Myometrium Reduces the Efficacy of Oxytocin but Not of Ergonovine Maleate or Prostaglandin F2α. Reprod. Sci. 17, 269–277 (2010). https://doi.org/10.1177/1933719109351934

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719109351934

Key words

Search

Navigation