Skip to main content

Advertisement

Log in

Pathophysiology of pre-eclampsia: Update on the role of nitric oxide

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Women with chronic hypertension and pregnancy-induced hypertension are at substantial risk for developing preeclampsia/ eclampsia, a disease with high fetomaternal morbidity and mortality. However, the etiology of this disease is still unknown. In this article, recent concepts on the pathophysiology of pre-eclampsia, with special attention to the role of nitric oxide, are reviewed.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Roberts JM, Pearson G, Cutler J, et al.: Summary of the NHLBI Working Group on Research on Hypertension During Pregnancy. Hypertension 2003, 41:437–45. Consensus on classification of hypertensive disorders of pregnancy and summary of recent insights into the pathophysiology of preeclampsia.

    Article  PubMed  CAS  Google Scholar 

  2. Sibai BM: Chronic hypertension in pregnancy. Obstet Gynecol 2002, 100:369–377.

    Article  PubMed  Google Scholar 

  3. Brown MA, Lindheimer MD, de Swiet M, et al.: The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregn 2001, 20:IX-XIV.

    Article  CAS  Google Scholar 

  4. Hallak M: Hypertension in pregnancy. In High Risk Pregnancy. Management Options. Edited by James DK, Steer PJ, Weiner CP, et al. Philadelphia: WB Saunders; 1999:639–663.

    Google Scholar 

  5. Zhang J, Klebanoff MA, Roberts JM: Prediction of adverse outcomes by common definitions of hypertension in pregnancy. Obstet Gynecol 2001, 97:261–267.

    Article  PubMed  CAS  Google Scholar 

  6. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000, 183:S1–S22.

  7. Sibai BM, Gordon T, Thom E, et al.: Risk factors for preeclampsia in healthy nulliparous women: a prospective multicenter study. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Am J Obstet Gynecol 1995, 172:642–648.

    Article  PubMed  CAS  Google Scholar 

  8. Seligman S: Which blood pressure? Br J Obstet Gynaecol 1987, 94:497–498.

    PubMed  CAS  Google Scholar 

  9. Weinstein L: Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy. Am J Obstet Gynecol 1982, 142:159–167.

    PubMed  CAS  Google Scholar 

  10. Sibai BM: The HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): much ado about nothing? Am J Obstet Gynecol 1990, 162:311–316.

    PubMed  CAS  Google Scholar 

  11. Shembrey MA, Noble AD: An instructive case of abdominal pregnancy. Aust N Z J Obstet Gynaecol 1995, 35:220–221.

    PubMed  CAS  Google Scholar 

  12. Page E: The relation between hydatidiform moles, relative ischemia of the gravid uterus, and the placental origin of eclampsia. Am J Obstet Gynecol 1939, 37:291–293.

    Google Scholar 

  13. Roberts JM, Lain KY: Recent insights into the pathogenesis of pre-eclampsia. Placenta 2002, 23:359–372.

    Article  PubMed  CAS  Google Scholar 

  14. Baylis C, Beinder E, Suto T, et al.: Recent insights into the roles of nitric oxide and renin-angiotensin in the pathophysiology of preeclamptic pregnancy. Semin Nephrol 1998, 18:208–230. A comprehensive overview on recent study results regarding the role of NO in normal and pre-eclamptic pregnancy.

    PubMed  CAS  Google Scholar 

  15. Scalera F, Schlembach D, Beinder E: Production of vasoactive substances by human umbilical vein endothelial cells after incubation with serum from preeclamptic patients. Eur J Obstet Gynecol Reprod Biol 2001, 99:172–178.

    Article  PubMed  CAS  Google Scholar 

  16. Savvidou MD, Hingorani A, Tsikas D, et al.: Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre-eclampsia. Lancet 2003, 361:1511–17. Important study demonstrating the correlation between NO deficiency and disturbed maternofetal circulation.

    Article  PubMed  CAS  Google Scholar 

  17. Clark SL, Cotton DB, Lee W, et al.: Central hemodynamic assessment of normal term pregnancy. Am J Obstet Gynecol 1989, 161:1439–1442.

    PubMed  CAS  Google Scholar 

  18. Roberts M, Lindeheimer MD, Davison JM: Altered glomerular permselectivity to neutral dextrans and heteroporous membrane modeling in human pregnancy. Am J Physiol 1996, 270(2Pt2):F338-F343.

    PubMed  CAS  Google Scholar 

  19. Baylis C: Glomerular filtration and volume regulation in gravid animal models. Bailliere’s Clin Obstet Gynaecol 1994, 8:235–264.

    Article  CAS  Google Scholar 

  20. Cotton D, Lee W, Huhta J, et al.: Hemodynamic profile of severe pregnancy-induced hypertension. Am J Obstet Gynecol 1988, 158:523–529.

    PubMed  CAS  Google Scholar 

  21. Groenendijk R, Trimbos JB, Wallenburg HC: Hemodynamic measurements in preeclampsia: preliminary observations. Am J Obstet Gynecol 1984, 150:232–236.

    PubMed  CAS  Google Scholar 

  22. Brown M, Zammit V, Mitar D: Extracellular fluid volume in pregnancy-induced hypertension. J Hypertens 1992, 10:61–68.

    Article  PubMed  CAS  Google Scholar 

  23. Zhou Y, Damsky CH, Fisher SJ: Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype: one cause of defective endovascular invasion in this syndrome? J Clin Invest 1997, 99:2152–2164.

    Article  PubMed  CAS  Google Scholar 

  24. Reister F, Frank HG, Kingdom JC, et al.: Macrophage-induced apoptosis limits endovascular trophoblast invasion in the uterine wall of preeclamptic women. Lab Invest 2001, 81:1143–1152.

    PubMed  CAS  Google Scholar 

  25. Taylor RN, Grimwood J, Taylor RS, et al.: Longitudinal serum concentrations of placental growth factor: evidence for abnormal placental angiogenesis in pathologic pregnancies. Am J Obstet Gynecol 2003, 188:177–182.

    Article  PubMed  CAS  Google Scholar 

  26. Genbacev O, Zhou Y, Ludlow JW, et al.: Regulation of human placental development by oxygen tension. Science 1997, 277:1669–1672. The impact of oxygen tension on the proliferative capacity of cytotrophoblasts is demonstrated.

    Article  PubMed  CAS  Google Scholar 

  27. Kashiwagi M, Breymann C, Huch R, et al.: Hypertension in a pregnancy with renal anemia after recombinant human erythropoietin (rhEPO) therapy. Arch Gynecol Obstet 2002, 267:54–56.

    Article  PubMed  CAS  Google Scholar 

  28. Ong SS, Crocker IP, Warren AY, et al.: Functional characteristics of chorionic plate placental arteries from normal pregnant women and women with pre-eclampsia. Hypertens Pregnancy 2002, 21:175–183.

    Article  PubMed  Google Scholar 

  29. King RG, Gude NM, Di Iulio JL, et al.: Regulation of human placental fetal vessel tone: role of nitric oxide. Reprod Fertil Dev 1995, 7:1407–1411.

    Article  PubMed  CAS  Google Scholar 

  30. Walsh SW: Preeclampsia: an imbalance in placental prostacyclin and thromboxane production. Am J Obstet Gynecol 1985, 152:335–340.

    PubMed  CAS  Google Scholar 

  31. Chavarria ME, Lara-Gonzalez L, Gonzalez-Gleason A, et al.:Prostacyclin/thromboxane early changes in pregnancies that are complicated by preeclampsia. Am J Obstet Gynecol 2003, 188:986–992.

    Article  PubMed  CAS  Google Scholar 

  32. Scalera F, Dittrich R, Beckmann MW, et al.: Effect of endothelin-1 on intracellular glutathione and lipid peroxide availability and on the secretion of vasoactive substances by human umbilical vein endothelial cells. Eur J Clin Invest 2002, 32:556–562.

    Article  PubMed  CAS  Google Scholar 

  33. Cockell AP, Poston L: Flow-mediated vasodilatation is enhanced in normal pregnancy but reduced in preeclampsia. Hypertension 1997, 30:247–251.

    PubMed  CAS  Google Scholar 

  34. Li H, Wallerath T, Forstermann U: Physiological mechanisms regulating the expression of endothelial-type NO synthase. Nitric Oxide 2002, 7:132–147.

    Article  PubMed  CAS  Google Scholar 

  35. Sladek SM, Magness RR, Conrad KP: Nitric oxide and pregnancy. Am J Physiol 1997, 272:R441-R463.

    PubMed  CAS  Google Scholar 

  36. Seligman SP, Buyon JP, Clancy RM, et al.: The role of nitric oxide in the pathogenesis of preeclampsia. Am J Obstet Gynecol 1994, 171:944–948.

    PubMed  CAS  Google Scholar 

  37. Williams DJ, Vallance PJ, Neild GH, et al.: Nitric oxide-mediated vasodilation in human pregnancy. Am J Physiol 1997, 272:H748-H752.

    PubMed  CAS  Google Scholar 

  38. Conrad KP, Joffe GM, Kruszyna H, et al.: Identification of increased nitric oxide biosynthesis during pregnancy in rats. FASEB J 1993, 7:566–571.

    PubMed  CAS  Google Scholar 

  39. Myatt L, Brewer AS, Langdon G, et al.: Attenuation of the vasoconstrictor effects of thromboxane and endothelin by nitric oxide in the human fetal-placental circulation. Am J Obstet Gynecol 1992, 166:224–230.

    PubMed  CAS  Google Scholar 

  40. Cadnapaphornchai MA, Ohara M, Morris KG Jr, et al.: Chronic NOS inhibition reverses systemic vasodilation and glomerular hyperfiltration in pregnancy. Am J Physiol Renal Physiol 2001, 280:F592-F598.

    PubMed  CAS  Google Scholar 

  41. Diket AL, Pierce MR, Munshi UK, et al.: Nitric oxide inhibition causes intrauterine growth retardation and hind-limb disruptions in rats. Am J Obstet Gynecol 1994, 171:1243–1250.

    PubMed  CAS  Google Scholar 

  42. Yallampalli C, Garfield RE: Inhibition of nitric oxide synthesis in rats during pregnancy produces signs similar to those of preeclampsia. Am J Obstet Gynecol 1993, 169:1316–1320. This article reveals a possible correlation between NO deficiency and pre-eclampsia.

    PubMed  CAS  Google Scholar 

  43. Salas SP, Altermatt F, Campos M, et al.: Effects of long-term nitric oxide synthesis inhibition on plasma volume expansion and fetal growth in the pregnant rat. Hypertension 1995, 26:1019–1023. This study provided additional evidence for a correlation between NO deficiency and fetal intrauterine growth retardation, which is a common feature in early-onset pre-eclampsia.

    PubMed  CAS  Google Scholar 

  44. Molnar M, Suto T, Toth T, et al.: Prolonged blockade of nitric oxide synthesis in gravid rats produces sustained hypertension, proteinuria, thrombocytopenia, and intrauterine growth retardation. Am J Obstet Gynecol 1994, 170:1458–1466.

    PubMed  CAS  Google Scholar 

  45. Ramsay B, Sooranna SR, Johnson MR: Nitric oxide synthase activities in human myometrium and villous trophoblast throughout pregnancy. Obstet Gynecol 1996, 87:249–253.

    Article  PubMed  CAS  Google Scholar 

  46. Beinder E, Mohaupt MG, Schlembach D, et al.: Nitric oxide synthase activity and Doppler parameters in the fetoplacental and uteroplacental circulation in preeclampsia. Hypertens Pregn 1999, 18:115–127.

    CAS  Google Scholar 

  47. Shaamash AH, Elsnosy ED, Makhlouf AM, et al.: Maternal and fetal serum nitric oxide (NO) concentrations in normal pregnancy, pre-eclampsia and eclampsia. Int J Gynaecol Obstet 2000, 68:207–214.

    Article  PubMed  CAS  Google Scholar 

  48. Rajagopal M, Moodley J, Chetty R: Nitric oxide: Does it have an etiological role in pre-eclampsia? Acta Obstet Gynecol Scand 2003, 82:216–219.

    Article  PubMed  Google Scholar 

  49. Nakatsuka M, Takata M, Tada K, et al.: A long-term transdermal nitric oxide donor improves uteroplacental circulation in women with preeclampsia. J Ultrasound Med 2002, 21:831–836.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kashiwagi, M., Zimmermann, R. & Beinder, E. Pathophysiology of pre-eclampsia: Update on the role of nitric oxide. Current Science Inc 5, 493–497 (2003). https://doi.org/10.1007/s11906-003-0057-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-003-0057-2

Keywords

Navigation