Abstract
Objective
To elucidate the regulation of the nitric oxide (NO) and carbon monoxide (CO) pathways in preeclampsia and to evaluate the ratio of asymmetric dimethylarginine (ADMA) to symmetric dimethylarginine (SDMA) as a marker for preeclampsia.
Methods
Maternal plasma and placental samples were obtained from 20 participants with preeclampsia and 23 controls. Enzyme-linked immunosorbent assay was used to measure plasma NO, ADMA, and SDMA as well as placental NO and hemeoxygnase 1 (HO-1). Western blot was used to measure placental dimethylarginine dimethylaminotransferases (DDAH-I and DDAH-II).
Results
Placental DDAH-I, placental DDAH-II, placental NO, and placental HO-1 were significantly decreased in participants with preeclampsia. While ADMA and SDMA levels were decreased in preeclampsia, the ADMA-SDMA ratio was not significantly different.
Conclusions
Decreased DDAH and HO with preeclampsia suggest that they are important points in the regulatory pathways of NO and CO production that are altered in preeclampsia. The ADMA-SDMA ratio is not a useful test for preeclampsia.
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References
Sibai BM. Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol. 2003;102(1):181–192.
Merviel P, Carbillon L, Challier JC, Rabreau M, Beaufils M, Uzan S. Pathophysiology of preeclampsia: links with implantation disorders. Eur J Obstet Gynecol Reprod Biol. 2004;115(2):134–147.
Boger RH, Diemert A, Schwedhelm E, Luneburg N, Maas R, Hecher K. The role of nitric oxide synthase inhibition by asymmetric dimethylarginine in the pathophysiology of preeclampsia. Gynecol Obstet Invest. 2010;69(1):1–13.
Bainbridge SA, Smith GN. HO in pregnancy. Free Radic Biol Med. 2005;38(8):979–988.
Fickling SA, Williams D, Vallance P, Nussey SS, Whitley GS. Plasma concentrations of endogenous inhibitor of nitric oxide synthesis in normal pregnancy and pre-eclampsia. Lancet. 1993;342(8865):242–243.
Holden DP, Fickling SA, Whitley GS, Nussey SS. Plasma concentrations of asymmetric dimethylarginine, a natural inhibitor of nitric oxide synthase, in normal pregnancy and preeclampsia. Am J Obstet Gynecol. 1998;178(3):551–556.
Speer PD, Powers RW, Frank MP, Harger G, Markovic N, Roberts JM. Elevated asymmetric dimethylarginine concentrations precede clinical preeclampsia, but not pregnancies with small-for-gestational-age infants. Am J Obstet Gynecol. 2008;198(1):112.e1–112.e7.
Pettersson A, Hedner T, Milsom I. Increased circulating concentrations of asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, in preeclampsia. Acta Obstet Gynecol Scand. 1998;77(8):808–813.
Ellis J, Wennerholm UB, Bengtsson A, et al. Levels of dimethylarginines and cytokines in mild and severe preeclampsia. Acta Obstet Gynecol Scand. 2001;80(7):602–608.
Braekke K, Ueland PM, Harsem NK, Staff AC. Asymmetric dimethylarginine in the maternal and fetal circulation in preeclampsia. Pediatr Res 2009;66(4):411–415.
Mao D, Che J, Li K, et al. Association of homocysteine, asymmetric dimethylarginine, and nitric oxide with preeclampsia. Arch Gynecol Obstet. 2010;282(4):371–375.
Maas R, Boger RH, Schwedhelm E, et al. Plasma concentrations of asymmetric dimethylarginine (ADMA) in Colombian women with pre-eclampsia. JAMA. 2004;291(7):823–824.
Siroen MP, Teerlink T, Bolte AC, et al. No compensatory upregulation of placental dimethylarginine dimethylaminohydrolase activity in preeclampsia. Gynecol Obstet Invest 2006;62(1):7–13.
King RG, Di Iulio JL, Gude NM, Brennecke SP. Effect of asymmetric dimethyl arginine on nitric oxide synthase activity in normal and pre-eclamptic placentae. Reprod Fertil Dev 1995;7(6):1581–1584.
Pope AJ, Karuppiah K, Cardounel AJ. Role of the PRMT-DDAH-ADMA axis in the regulation of endothelial nitric oxide production. Pharmacol Res. 2009;60(6):461–465.
Ahmed A, Rahman M, Zhang X, et al. Induction of placental heme oxygenase-1 is protective against TNFalpha-induced cytotoxicity and promotes vessel relaxation. Mol Med. 2000;6(5):391–409.
Barber A, Robson SC, Myatt L, Bulmer JN, Lyall F. Heme oxygenase expression in human placenta and placental bed: reduced expression of placenta endothelial HO-2 in preeclampsia and fetal growth restriction. FASEB J. 2001;15(7): 1158–1168.
Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy. 2001;20(1): IX-XIV.
Liao WX, Magness RR, Chen DB. Expression of estrogen receptors-alpha and -beta in the pregnant ovine uterine artery endothelial cells in vivo and in vitro. Biol Reprod. 2005;72(3):530–537.
McLaughlin BE, Lash GE, Smith GN, et al. Heme Oxygenase Expression in Selected Regions of Term Human Placenta. Exp Biol Med. 2003;228(5):564–567.
Akbar F, Heinonen S, Pirskanen M, Uimari P, Tuomainen TP, Salonen JT. Haplotypic association of DDAH1 with susceptibility to pre-eclampsia. Mol Hum Reprod. 2005;11(1):73–77.
Vadillo-Ortega F, Perichart-Perera O, Espino S, et al. Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial. BMJ. 2011;342: d2901.
Rytlewski K, Olszanecki R, Korbut R, Zdebski Z. Effects of prolonged oral supplementation with L-arginine on blood pressure and nitric oxide synthesis in preeclampsia. Eur J Clin Invest. 2005;35(1):32–37.
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Ehsanipoor, R.M., Fortson, W., Fitzmaurice, L.E. et al. Nitric Oxide and Carbon Monoxide Production and Metabolism in Preeclampsia. Reprod. Sci. 20, 542–548 (2013). https://doi.org/10.1177/1933719112459231
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DOI: https://doi.org/10.1177/1933719112459231