Abstract
In preeclampsia, the shallow invasion of cytotrophoblast cells to uterine spiral arteries, leading to a reduction in placental blood flow, is associated with an imbalance of proangiogenic/antiangiogenic factors to impaired nitric oxide (NO) production. Proangiogenic factors, such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), require NO to induce angiogenesis through antioxidant regulation mechanisms. At the same time, there are increases in antiangiogenic factors in preeclampsia, such as soluble fms-like tyrosine kinase type 1 receptor (sFIt1) and toll-like receptor 9 (TLR9), which are mechanism derivates in the reduction of NO bioavailability and oxidative stress in placenta.
Different strategies have been proposed to prevent or alleviate the detrimental effects of preeclampsia. However, the only intervention to avoid the severe consequences of the disease is the interruption of pregnancy. In this scenario, different approaches have been analysed to treat preeclamptic pregnant women safely. The supplementation with amino acids is one of them, especially those associated with NO synthesis. In this review, we discuss emerging concepts in the pathogenesis of preeclampsia to highlight L-arginine and L-citrulline supplementation as potential strategies to improve birth outcomes. Clinical and experimental data concerning L-arginine and L-citrulline supplementation have shown benefits in improving NO availability in the placenta and uterine-placental circulation, prolonging pregnancy in patients with gestational hypertension and decreasing maternal blood pressure.
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References
Abalos E, Duley L, Steyn DW, Gialdini C (2018) Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD002252.pub4
Acauan Filho BJ, Pinheiro da Costa BE, Ogando PB, Vieira MC, Antonello IC, Poli-de-Figueiredo CE (2016) Serum nitrate and NOx levels in preeclampsia are higher than in normal pregnancy. Hypertens Pregnancy 35:226–233. https://doi.org/10.3109/10641955.2016.1139718
ACOG Committee on Obstetric Practice (2002) ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 77:67–75
Ahmad S, Ahmed A (2004) Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits angiogenesis in preeclampsia. Circ Res 95:884–891. https://doi.org/10.1161/01.RES.0000147365.86159.f5
Alexander BT, Miller MT, Kassab S, Novak J, Reckelhoff JF, Kruckeberg WC, Granger JP (1999) Differential expression of renal nitric oxide synthase isoforms during pregnancy in rats. Hypertens Dallas Tex 1979(33):435–439. https://doi.org/10.1161/01.hyp.33.1.435
Alexander BT, Kassab SE, Miller MT, Abram SR, Reckelhoff JF, Bennett WA, Granger JP (2001) Reduced uterine perfusion pressure during pregnancy in the rat is associated with increases in arterial pressure and changes in renal nitric oxide. Hypertens Dallas Tex 1979(37):1191–1195. https://doi.org/10.1161/01.hyp.37.4.1191
Alexander BT, Llinas MT, Kruckeberg WC, Granger JP (2004) L-arginine attenuates hypertension in pregnant rats with reduced uterine perfusion pressure. Hypertens Dallas Tex 1979(43):832–836. https://doi.org/10.1161/01.HYP.0000119192.32360.a9
Almasry SM, Elfayomy AK, Hashem HE (2016) Ultrastructure and histomorphometric analysis of human umbilical cord vessels in preeclampsia: a potential role of VEGF, VEGFR-1 and VEGFR-2. Romanian J Morphol Embryol/Rev Roum Morphol Embryol 57:681–689
Alvares TS, Conte-Junior CA, Silva JT, Paschoalin VMF (2012) Acute L-Arginine supplementation does not increase nitric oxide production in healthy subjects. Nutr Metab 9:54. https://doi.org/10.1186/1743-7075-9-54
Amaral TAS, Ognibene DT, Carvalho LCRM, Rocha APM, Costa CA, Moura RS, Resende AC (2018) Differential responses of mesenteric arterial bed to vasoactive substances in L-NAME-induced preeclampsia: role of oxidative stress and endothelial dysfunction. Clin Exp Hypertens N Y N 1993(40):126–135. https://doi.org/10.1080/10641963.2017.1339073
Arikawe AP, Udenze IC, Olusanya AW, Akinnibosun OA, Dike I, Duru BN (2019) L-arginine supplementation lowers blood pressure, protein excretion and plasma lipid profile in experimental salt-induced hypertension in pregnancy: relevance to preeclampsia. Pathophysiology 26:191–197. https://doi.org/10.1016/j.pathophys.2019.02.002
Arvizu M, Afeiche MC, Hansen S, Halldorsson TF, Olsen SF, Chavarro JE (2019) Fat intake during pregnancy and risk of preeclampsia: a prospective cohort study in Denmark. Eur J Clin Nutr 73:1040–1048. https://doi.org/10.1038/s41430-018-0290-z
Backes CH, Markham K, Moorehead P, Cordero L, Nankervis CA, Giannone PJ (2011) Maternal preeclampsia and neonatal outcomes. J Pregnancy 2011:e214365. https://doi.org/10.1155/2011/214365
Barra S, Cachulo M do C, Providência R, Leitão-Marques A (2012) Hypertension in pregnancy: the current state of the art. Rev Port Cardiol Engl Ed 31:425–432. https://doi.org/10.1016/j.repce.2012.01.016
Basaran A, Basaran M, Topatan B (2010) Combined vitamin C and E supplementation for the prevention of preeclampsia: a systematic review and meta-analysis. Obstet Gynecol Surv 65:653–667. https://doi.org/10.1097/OGX.0b013e3182095366
Beazley D, Ahokas R, Livingston J, Griggs M, Sibai BM (2005) Vitamin C and E supplementation in women at high risk for preeclampsia: a double-blind, placebo-controlled trial. Am J Obstet Gynecol 192:520–521. https://doi.org/10.1016/j.ajog.2004.09.005
Bergman L, Acurio J, Leon J, Gatu E, Friis T, Nelander M, Wikström J, Larsson A, Lara E, Aguayo C, Torres-Vergara P, Wikström A-K, Escudero C (2021) Preeclampsia and increased permeability over the blood-brain barrier: a role of vascular endothelial growth receptor 2. Am J Hypertens 34:73–81. https://doi.org/10.1093/ajh/hpaa142
Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, de Onis M, Ezzati M, Grantham-McGregor S, Katz J, Martorell R, Uauy R, Maternal and Child Nutrition Study Group (2013) Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet Lond Engl 382:427–451. https://doi.org/10.1016/S0140-6736(13)60937-X
Böger RH, Diemert A, Schwedhelm E, Lüneburg N, Maas R, Hecher K (2010) The role of nitric oxide synthase inhibition by asymmetric dimethylarginine in the pathophysiology of preeclampsia. Gynecol Obstet Investig 69:1–13. https://doi.org/10.1159/000245940
Bourdon A, Parnet P, Nowak C, Tran N-T, Winer N, Darmaun D (2016) L-Citrulline supplementation enhances fetal growth and protein synthesis in rats with intrauterine growth restriction. J Nutr 146:532–541. https://doi.org/10.3945/jn.115.221267
Bowen RS, Zhang Y, Gu Y, Lewis DF, Wang Y (2005) Increased phospholipase A2 and thromboxane but not prostacyclin production by placental trophoblast cells from normal and preeclamptic pregnancies cultured under hypoxia condition. Placenta 26:402–409. https://doi.org/10.1016/j.placenta.2004.07.007
Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, Hall DR, Warren CE, Adoyi G, Ishaku S, International Society for the Study of Hypertension in Pregnancy (ISSHP) (2018) The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens 13:291–310. https://doi.org/10.1016/j.preghy.2018.05.004
Burton GJ, Redman CW, Roberts JM, Moffett A (2019) Pre-eclampsia: pathophysiology and clinical implications. BMJ 366:l2381. https://doi.org/10.1136/bmj.l2381
Bussolati B, Dunk C, Grohman M, Kontos CD, Mason J, Ahmed A (2001) Vascular endothelial growth factor receptor-1 modulates vascular endothelial growth factor-mediated angiogenesis via nitric oxide. Am J Pathol 159:993–1008. https://doi.org/10.1016/S0002-9440(10)61775-0
Casanello P, Sobrevia L (2002) Intrauterine growth retardation is associated with reduced activity and expression of the cationic amino acid transport systems y+/hCAT-1 and y+/hCAT-2B and lower activity of nitric oxide synthase in human umbilical vein endothelial cells. Circ Res 91:127–134. https://doi.org/10.1161/01.res.0000027813.55750.e7
Casanello P, Krause B, Torres E, Gallardo V, González M, Prieto C, Escudero C, Farías M, Sobrevia L (2009) Reduced l-arginine transport and nitric oxide synthesis in human umbilical vein endothelial cells from intrauterine growth restriction pregnancies is not further altered by hypoxia. Placenta 30:625–633. https://doi.org/10.1016/j.placenta.2009.04.010
Chaiworapongsa T, Chaemsaithong P, Yeo L, Romero R (2014) Pre-eclampsia part 1: current understanding of its pathophysiology. Nat Rev Nephrol 10:466–480. https://doi.org/10.1038/nrneph.2014.102
Chakraborty D, Cui W, Rosario GX, Scott RL, Dhakal P, Renaud SJ, Tachibana M, Rumi MAK, Mason CW, Krieg AJ, Soares MJ (2016) HIF-KDM3A-MMP12 regulatory circuit ensures trophoblast plasticity and placental adaptations to hypoxia. Proc Natl Acad Sci U S A 113:E7212–E7221. https://doi.org/10.1073/pnas.1612626113
Chambers JC, Fusi L, Malik IS, Haskard DO, De Swiet M, Kooner JS (2001) Association of maternal endothelial dysfunction with preeclampsia. JAMA 285:1607–1612. https://doi.org/10.1001/jama.285.12.1607
Chau K, Hennessy A, Makris A (2017) Placental growth factor and pre-eclampsia. J Hum Hypertens 31:782–786. https://doi.org/10.1038/jhh.2017.61
Chen Z-W, Huang Y, Yang Q, Li X, Wei W, He G-W (2005) Urocortin-induced relaxation in the human internal mammary artery. Cardiovasc Res 65:913–920. https://doi.org/10.1016/j.cardiores.2004.11.018
Chen H, Li J, Li N, Liu H, Tang J (2019) Increased circulating trimethylamine N-oxide plays a contributory role in the development of endothelial dysfunction and hypertension in the RUPP rat model of preeclampsia. Hypertens Pregnancy 38:96–104. https://doi.org/10.1080/10641955.2019.1584630
Chu ZM, Beilin LJ (1993) Mechanisms of vasodilatation in pregnancy: studies of the role of prostaglandins and nitric-oxide in changes of vascular reactivity in the in situ blood perfused mesentery of pregnant rats. Br J Pharmacol 109:322–329. https://doi.org/10.1111/j.1476-5381.1993.tb13573.x
Conrad KP, Joffe GM, Kruszyna H, Kruszyna R, Rochelle LG, Smith RP, Chavez JE, Mosher MD (1993) Identification of increased nitric oxide biosynthesis during pregnancy in rats. FASEB J 7:566–571
Cubro H, Kashyap S, Nath MC, Ackerman AW, Garovic VD (2018) The role of interleukin-10 in the pathophysiology of preeclampsia. Curr Hypertens Rep 20:36. https://doi.org/10.1007/s11906-018-0833-7
Cudmore M, Ahmad S, Al-Ani B, Hewett P, Ahmed S, Ahmed A (2006) VEGF-E activates endothelial nitric oxide synthase to induce angiogenesis via cGMP and PKG-independent pathways. Biochem Biophys Res Commun 345:1275–1282. https://doi.org/10.1016/j.bbrc.2006.04.031
Davison JM, Homuth V, Jeyabalan A, Conrad KP, Karumanchi SA, Quaggin S, Dechend R, Luft FC (2004) New aspects in the pathophysiology of preeclampsia. J Am Soc Nephrol JASN 15:2440–2448. https://doi.org/10.1097/01.ASN.0000135975.90889.60
Donoso Siña E (2011) TRAS EL CUMPLIMIENTO DEL 5o OBJETIVO DEL MILENIO: MORTALIDAD MATERNA, Chile 2008. Rev Chil Obstet Ginecol 76:1–2. https://doi.org/10.4067/S0717-75262011000100001
Dover N, Gulerman HC, Celen S, Kahyaoglu S, Yenicesu O (2013) Placental growth factor: as an early second trimester predictive marker for preeclampsia in normal and high-risk pregnancies in a Turkish population. J Obstet Gynaecol India 63:158–163. https://doi.org/10.1007/s13224-012-0279-9
Eiland E, Nzerue C, Faulkner M (2012) Preeclampsia. J Pregnancy 2012:586578. https://doi.org/10.1155/2012/586578
Erez O, Romero R, Espinoza J, Fu W, Todem D, Kusanovic JP, Gotsch F, Edwin S, Nien JK, Chaiworapongsa T, Mittal P, Mazaki-Tovi S, Than NG, Gomez R, Hassan SS (2008) The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age. J Matern-Fetal Neonatal Med 21:279–287. https://doi.org/10.1080/14767050802034545
Estrategia Nacional de Salud 2011-2020 [WWW Document] (n.d.) Serv. Salud Ñuble. https://www.serviciodesaludnuble.cl/sitio/estrategia-nacional-de-salud-2011-2020/. Accessed 28 June 22
Evans RW, Fernstrom JD, Thompson J, Morris SM, Kuller LH (2004) Biochemical responses of healthy subjects during dietary supplementation with L-arginine. J Nutr Biochem 15:534–539. https://doi.org/10.1016/j.jnutbio.2004.03.005
Facchinetti F, Saade GR, Neri I, Pizzi C, Longo M, Volpe A (2007) L-arginine supplementation in patients with gestational hypertension: a pilot study. Hypertens Pregnancy 26:121–130. https://doi.org/10.1080/10641950601147994
Fan X, Rai A, Kambham N, Sung JF, Singh N, Petitt M, Dhal S, Agrawal R, Sutton RE, Druzin ML, Gambhir SS, Ambati BK, Cross JC, Nayak NR (2014) Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications. J Clin Invest 124:4941–4952. https://doi.org/10.1172/JCI76864
Figueroa A, Sanchez-Gonzalez MA, Perkins-Veazie PM, Arjmandi BH (2011) Effects of watermelon supplementation on aortic blood pressure and wave reflection in individuals with prehypertension: a pilot study. Am J Hypertens 24:40–44. https://doi.org/10.1038/ajh.2010.142
Flam BR, Eichler DC, Solomonson LP (2007) Endothelial nitric oxide production is tightly coupled to the citrulline-NO cycle. Nitric Oxide Biol Chem 17:115–121. https://doi.org/10.1016/j.niox.2007.07.001
Fushima T, Sekimoto A, Minato T, Ito T, Oe Y, Kisu K, Sato E, Funamoto K, Hayase T, Kimura Y, Ito S, Sato H, Takahashi N (2016) Reduced uterine perfusion pressure (RUPP) model of preeclampsia in mice. PLoS One 11:e0155426. https://doi.org/10.1371/journal.pone.0155426
Garg P, Jaryal AK, Kachhawa G, Deepak KK, Kriplani A (2018) Estimation of asymmetric dimethylarginine (ADMA), placental growth factor (PLGF) and pentraxin 3 (PTX 3) in women with preeclampsia. Pregnancy Hypertens 14:245–251. https://doi.org/10.1016/j.preghy.2018.03.005
Gélinas DS, Bernatchez PN, Rollin S, Bazan NG, Sirois MG (2002) Immediate and delayed VEGF-mediated NO synthesis in endothelial cells: role of PI3K, PKC and PLC pathways. Br J Pharmacol 137:1021–1030. https://doi.org/10.1038/sj.bjp.0704956
Gemmel M, Sutton EF, Brands J, Burnette L, Gallaher MJ, Powers RW (2021) L-Citrulline supplementation during pregnancy improves perinatal and postpartum maternal vascular function in a mouse model of preeclampsia. Am J Phys Regul Integr Comp Phys 321:R3364–RR376. https://doi.org/10.1152/ajpregu.00115.2020
Genbacev O, Joslin R, Damsky CH, Polliotti BM, Fisher SJ (1996) Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occur in preeclampsia. J Clin Invest 97:540–550. https://doi.org/10.1172/JCI118447
Geusens N, Verlohren S, Luyten C, Taube M, Hering L, Vercruysse L, Hanssens M, Dudenhausen JW, Dechend R, Pijnenborg R (2008) Endovascular trophoblast invasion, spiral artery remodelling and uteroplacental haemodynamics in a transgenic rat model of pre-eclampsia. Placenta 29:614–623. https://doi.org/10.1016/j.placenta.2008.04.005
Geusens N, Hering L, Verlohren S, Luyten C, Drijkoningen K, Taube M, Vercruysse L, Hanssens M, Dechend R, Pijnenborg R (2010) Changes in endovascular trophoblast invasion and spiral artery remodelling at term in a transgenic preeclamptic rat model. Placenta 31:320–326. https://doi.org/10.1016/j.placenta.2010.01.011
Gilbert JS, Babcock SA, Granger JP (2007) Hypertension produced by reduced uterine perfusion in pregnant rats is associated with increased soluble fms-like tyrosine kinase-1 expression. Hypertens Dallas Tex 1979(50):1142–1147. https://doi.org/10.1161/HYPERTENSIONAHA.107.096594
Gilbert JS, Ryan MJ, LaMarca BB, Sedeek M, Murphy SR, Granger JP (2008) Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction. Am J Physiol Heart Circ Physiol 294:H541–H550. https://doi.org/10.1152/ajpheart.01113.2007
González M, Flores C, Pearson JD, Casanello P, Sobrevia L (2004) Cell signalling-mediating insulin increase of mRNA expression for cationic amino acid transporters-1 and -2 and membrane hyperpolarization in human umbilical vein endothelial cells. Pflugers Arch 448:383–394. https://doi.org/10.1007/s00424-004-1261-x
González M, Gallardo V, Rodríguez N, Salomón C, Westermeier F, Guzmán-Gutiérrez E, Abarzúa F, Leiva A, Casanello P, Sobrevia L (2011a) Insulin-stimulated L-arginine transport requires SLC7A1 gene expression and is associated with human umbilical vein relaxation. J Cell Physiol 226:2916–2924. https://doi.org/10.1002/jcp.22635
González M, Muñoz E, Puebla C, Guzmán-Gutiérrez E, Cifuentes F, Nien J, Abarzua F, Leiva A, Casanello P, Sobrevia L (2011b) Maternal and fetal metabolic dysfunction in pregnancy diseases associated with vascular oxidative and nitrative stress. In: The molecular basis for the link between maternal health and the origin of fetal congenital abnormalities: an overview of association with oxidative stress. Bentham Science, pp 98–115
Granger JP, Alexander BT (2000) Abnormal pressure-natriuresis in hypertension: role of nitric oxide. Acta Physiol Scand 168:161–168. https://doi.org/10.1046/j.1365-201x.2000.00655.x
Granger JP, Alexander BT, Llinas MT, Bennett WA, Khalil RA (2002) Pathophysiology of preeclampsia: linking placental ischemia/hypoxia with microvascular dysfunction. Microcirc N Y N 1994(9):147–160. https://doi.org/10.1038/sj.mn.7800137
Groesch KA, Torry RJ, Wilber AC, Abrams R, Bieniarz A, Guilbert LJ, Torry DS (2011) Nitric oxide generation affects pro- and anti-angiogenic growth factor expression in primary human trophoblast. Placenta 32:926–931. https://doi.org/10.1016/j.placenta.2011.08.008
Gu Y, Lewis DF, Wang Y (2008) Placental productions and expressions of soluble endoglin, soluble fms-like tyrosine kinase receptor-1, and placental growth factor in normal and preeclamptic pregnancies. J Clin Endocrinol Metab 93:260–266. https://doi.org/10.1210/jc.2007-1550
Gui S, Jia J, Niu X, Bai Y, Zou H, Deng J, Zhou R (2014) Arginine supplementation for improving maternal and neonatal outcomes in hypertensive disorder of pregnancy: a systematic review. J Renin-Angiotensin-Aldosterone Syst JRAAS 15:88–96. https://doi.org/10.1177/1470320313475910
He H, Venema VJ, Gu X, Venema RC, Marrero MB, Caldwell RB (1999) Vascular endothelial growth factor signals endothelial cell production of nitric oxide and prostacyclin through flk-1/KDR activation of c-Src. J Biol Chem 274:25130–25135. https://doi.org/10.1074/jbc.274.35.25130
He B, Yang X, Li Y, Huang D, Xu X, Yang W, Dai Y, Zhang H, Chen Z, Cheng W (2018a) TLR9 (toll-like receptor 9) agonist suppresses angiogenesis by differentially regulating VEGFA (vascular endothelial growth factor a) and sFLT1 (soluble vascular endothelial growth factor receptor 1) in preeclampsia. Hypertens Dallas Tex 1979 71:671–680. https://doi.org/10.1161/HYPERTENSIONAHA.117.10510
He M, Li F, Yang M, Fan Y, Beejadhursing R, Xie Y, Zhou Y, Deng D (2018b) Impairment of BKca channels in human placental chorionic plate arteries is potentially relevant to the development of preeclampsia. Hypertens Res 41:126–134. https://doi.org/10.1038/hr.2017.99
Hidayat D, Fitriasari TM, Djuwantono T, Hidayat YM, Irianti S, Ritonga MA, Sunardi S (2022) L-Citrulline level in pregnant adolescent with severe preeclampsia compared to without preeclampsia: a cross-sectional study. Int J Womens Health Reprod Sci 10:11–15. https://doi.org/10.15296/ijwhr.2022.03
Hodžić J, Izetbegović S, Muračević B, Iriškić R, Štimjanin Jović H (2017) Nitric oxide biosynthesis during normal pregnancy and pregnancy complicated by preeclampsia. Med Glas 14:211–217. https://doi.org/10.17392/915-17
Holland OJ, Cuffe JSM, Dekker Nitert M, Callaway L, Kwan Cheung KA, Radenkovic F, Perkins AV (2018) Placental mitochondrial adaptations in preeclampsia associated with progression to term delivery. Cell Death Dis 9:1150. https://doi.org/10.1038/s41419-018-1190-9
Hsu C-N, Tain Y-L (2019) Impact of arginine nutrition and metabolism during pregnancy on offspring outcomes. Nutrients 11:E1452. https://doi.org/10.3390/nu11071452
Jardim LL, Rios DRA, Perucci LO, de Sousa LP, Gomes KB, Dusse LMS (2015) Is the imbalance between pro-angiogenic and anti-angiogenic factors associated with preeclampsia? Clin Chim Acta Int J Clin Chem 447:34–38. https://doi.org/10.1016/j.cca.2015.05.004
Jeyabalan A, Conrad KP (2007) Renal function during normal pregnancy and preeclampsia. Front Biosci J Virtual Libr 12:2425–2437. https://doi.org/10.2741/2244
Ji L, Brkić J, Liu M, Fu G, Peng C, Wang Y-L (2013) Placental trophoblast cell differentiation: physiological regulation and pathological relevance to preeclampsia. Mol Asp Med 34:981–1023. https://doi.org/10.1016/j.mam.2012.12.008
Jia N, Li J (2020) Human uterine decidual NK cells in women with a history of early pregnancy enhance angiogenesis and trophoblast invasion. Biomed Res Int 2020:6247526. https://doi.org/10.1155/2020/6247526
Jones ML, Mark PJ, Waddell BJ (2014) Maternal dietary omega-3 fatty acids and placental function. Reprod Camb Engl 147:R143–R152. https://doi.org/10.1530/REP-13-0376
Karteris E, Vatish M, Hillhouse EW, Grammatopoulos DK (2005) Preeclampsia is associated with impaired regulation of the placental nitric oxide-cyclic guanosine monophosphate pathway by corticotropin-releasing hormone (CRH) and CRH-related peptides. J Clin Endocrinol Metab 90:3680–3687. https://doi.org/10.1210/jc.2004-2210
Karthikeyan VJ, Lip GYH (2007) Hypertension in pregnancy: pathophysiology and management strategies. Curr Pharm Des 13:2567–2579. https://doi.org/10.2174/138161207781663019
Karumanchi SA, Maynard SE, Stillman IE, Epstein FH, Sukhatme VP (2005) Preeclampsia: a renal perspective. Kidney Int 67:2101–2113. https://doi.org/10.1111/j.1523-1755.2005.00316.x
Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C, Heuton KR, Gonzalez-Medina D, Barber R, Huynh C, Dicker D, Templin T, Wolock TM, Ozgoren AA, Abd-Allah F, Abera SF, Abubakar I, Achoki T, Adelekan A, Ademi Z, Adou AK, Adsuar JC, Agardh EE, Akena D, Alasfoor D, Alemu ZA, Alfonso-Cristancho R, Alhabib S, Ali R, Al Kahbouri MJ, Alla F, Allen PJ, AlMazroa MA, Alsharif U, Alvarez E, Alvis-Guzmán N, Amankwaa AA, Amare AT, Amini H, Ammar W, Antonio CAT, Anwari P, Arnlöv J, Arsenijevic VSA, Artaman A, Asad MM, Asghar RJ, Assadi R, Atkins LS, Badawi A, Balakrishnan K, Basu A, Basu S, Beardsley J, Bedi N, Bekele T, Bell ML, Bernabe E, Beyene TJ, Bhutta Z, Bin Abdulhak A, Blore JD, Basara BB, Bose D, Breitborde N, Cárdenas R, Castañeda-Orjuela CA, Castro RE, Catalá-López F, Cavlin A, Chang J-C, Che X, Christophi CA, Chugh SS, Cirillo M, Colquhoun SM, Cooper LT, Cooper C, da Costa Leite I, Dandona L, Dandona R, Davis A, Dayama A, Degenhardt L, De Leo D, del Pozo-Cruz B, Deribe K, Dessalegn M, deVeber GA, Dharmaratne SD, Dilmen U, Ding EL, Dorrington RE, Driscoll TR, Ermakov SP, Esteghamati A, Faraon EJA, Farzadfar F, Felicio MM, Fereshtehnejad S-M, de Lima GMF, Forouzanfar MH, França EB, Gaffikin L, Gambashidze K, Gankpé FG, Garcia AC, Geleijnse JM, Gibney KB, Giroud M, Glaser EL, Goginashvili K, Gona P, González-Castell D, Goto A, Gouda HN, Gugnani HC, Gupta R, Gupta R, Hafezi-Nejad N, Hamadeh RR, Hammami M, Hankey GJ, Harb HL, Havmoeller R, Hay SI, Pi IBH, Hoek HW, Hosgood HD, Hoy DG, Husseini A, Idrisov BT, Innos K, Inoue M, Jacobsen KH, Jahangir E, Jee SH, Jensen PN, Jha V, Jiang G, Jonas JB, Juel K, Kabagambe EK, Kan H, Karam NE, Karch A, Karema CK, Kaul A, Kawakami N, Kazanjan K, Kazi DS, Kemp AH, Kengne AP, Kereselidze M, Khader YS, Khalifa SEAH, Khan EA, Khang Y-H, Knibbs L, Kokubo Y, Kosen S, Defo BK, Kulkarni C, Kulkarni VS, Kumar GA, Kumar K, Kumar RB, Kwan G, Lai T, Lalloo R, Lam H, Lansingh VC, Larsson A, Lee J-T, Leigh J, Leinsalu M, Leung R, Li X, Li Y, Li Y, Liang J, Liang X, Lim SS, Lin H-H, Lipshultz SE, Liu S, Liu Y, Lloyd BK, London SJ, Lotufo PA, Ma J, Ma S, Machado VMP, Mainoo NK, Majdan M, Mapoma CC, Marcenes W, Marzan MB, Mason-Jones AJ, Mehndiratta MM, Mejia-Rodriguez F, Memish ZA, Mendoza W, Miller TR, Mills EJ, Mokdad AH, Mola GL, Monasta L, de la Cruz Monis J, Hernandez JCM, Moore AR, Moradi-Lakeh M, Mori R, Mueller UO, Mukaigawara M, Naheed A, Naidoo KS, Nand D, Nangia V, Nash D, Nejjari C, Nelson RG, Neupane SP, Newton CR, Ng M, Nieuwenhuijsen MJ, Nisar MI, Nolte S, Norheim OF, Nyakarahuka L, Oh I-H, Ohkubo T, Olusanya BO, Omer SB, Opio JN, Orisakwe OE, Pandian JD, Papachristou C, Park J-H, Caicedo AJP, Patten SB, Paul VK, Pavlin BI, Pearce N, Pereira DM, Pesudovs K, Petzold M, Poenaru D, Polanczyk GV, Polinder S, Pope D, Pourmalek F, Qato D, Quistberg DA, Rafay A, Rahimi K, Rahimi-Movaghar V, ur Rahman S, Raju M, Rana SM, Refaat A, Ronfani L, Roy N, Pimienta TGS, Sahraian MA, Salomon JA, Sampson U, Santos IS, Sawhney M, Sayinzoga F, Schneider IJC, Schumacher A, Schwebel DC, Seedat S, Sepanlou SG, Servan-Mori EE, Shakh-Nazarova M, Sheikhbahaei S, Shibuya K, Shin HH, Shiue I, Sigfusdottir ID, Silberberg DH, Silva AP, Singh JA, Skirbekk V, Sliwa K, Soshnikov SS, Sposato LA, Sreeramareddy CT, Stroumpoulis K, Sturua L, Sykes BL, Tabb KM, Talongwa RT, Tan F, Teixeira CM, Tenkorang EY, Terkawi AS, Thorne-Lyman AL, Tirschwell DL, Towbin JA, Tran BX, Tsilimbaris M, Uchendu US, Ukwaja KN, Undurraga EA, Uzun SB, Vallely AJ, van Gool CH, Vasankari TJ, Vavilala MS, Venketasubramanian N, Villalpando S, Violante FS, Vlassov VV, Vos T, Waller S, Wang H, Wang L, Wang X, Wang Y, Weichenthal S, Weiderpass E, Weintraub RG, Westerman R, Wilkinson JD, Woldeyohannes SM, Wong JQ, Wordofa MA, Xu G, Yang YC, Yano Y, Yentur GK, Yip P, Yonemoto N, Yoon S-J, Younis MZ, Yu C, Jin KY, El Sayed Zaki M, Zhao Y, Zheng Y, Zhou M, Zhu J, Zou XN, Lopez AD, Naghavi M, Murray CJL, Lozano R (2014) Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet Lond Engl 384:980–1004. https://doi.org/10.1016/S0140-6736(14)60696-6
Kawasaki K, Smith RS, Hsieh C-M, Sun J, Chao J, Liao JK (2003) Activation of the phosphatidylinositol 3-kinase/protein kinase Akt pathway mediates nitric oxide-induced endothelial cell migration and angiogenesis. Mol Cell Biol 23:5726–5737. https://doi.org/10.1128/MCB.23.16.5726-5737.2003
Kharitonov SA, Lubec G, Lubec B, Hjelm M, Barnes PJ (1995) L-arginine increases exhaled nitric oxide in normal human subjects. Clin Sci 88:135–139. https://doi.org/10.1042/cs0880135
Kohli R, Meininger CJ, Haynes TE, Yan W, Self JT, Wu G (2004) Dietary l-arginine supplementation enhances endothelial nitric oxide synthesis in streptozotocin-induced diabetic rats. J Nutr 134:600–608. https://doi.org/10.1093/jn/134.3.600
Krueger J, Liu D, Scholz K, Zimmer A, Shi Y, Klein C, Siekmann A, Schulte-Merker S, Cudmore M, Ahmed A, le Noble F (2011) Flt1 acts as a negative regulator of tip cell formation and branching morphogenesis in the zebrafish embryo. Dev Camb Engl 138:2111–2120. https://doi.org/10.1242/dev.063933
La Marca-Ghaemmaghami P, Dainese SM, Stalla G, Haller M, Zimmermann R, Ehlert U (2017) Second-trimester amniotic fluid corticotropin-releasing hormone and urocortin in relation to maternal stress and fetal growth in human pregnancy. Stress Amst Neth 20:231–240. https://doi.org/10.1080/10253890.2017.1312336
Lassi ZS, Padhani ZA, Rabbani A, Rind F, Salam RA, Bhutta ZA (2021) Effects of nutritional interventions during pregnancy on birth, child health and development outcomes: a systematic review of evidence from low- and middle-income countries. Campbell Syst Rev 17. https://doi.org/10.1002/cl2.1150
Levine RJ, Maynard SE, Qian C, Lim K-H, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA (2004) Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 350:672–683. https://doi.org/10.1056/NEJMoa031884
Li F-F, He M-Z, Xie Y, Wu Y-Y, Yang M-T, Fan Y, Qiao F-Y, Deng D-R (2017) Involvement of dysregulated IKCa and SKCa channels in preeclampsia. Placenta 58:9–16. https://doi.org/10.1016/j.placenta.2017.07.361
Lu Y-R, Zhang Y, Rao Y-B, Chen X, Lou H-F, Zhang Y, Xie H-Y, Fang P, Hu L-W (2018) The changes in, and relationship between, plasma nitric oxide and corticotropin-releasing hormone in patients with major depressive disorder. Clin Exp Pharmacol Physiol 45:10–15. https://doi.org/10.1111/1440-1681.12826
MacKenzie A, Wadsworth RM (2003) Extracellular L-arginine is required for optimal NO synthesis by eNOS and iNOS in the rat mesenteric artery wall. Br J Pharmacol 139:1487–1497. https://doi.org/10.1038/sj.bjp.0705380
Magee LA, Pels A, Helewa M, Rey E, von Dadelszen P, SOGC Hypertension Guideline Committee (2014) Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy: executive summary. J Obstet Gynecol Can JOGC 36:575–576. https://doi.org/10.1016/S1701-2163(15)30533-8
Makrigiannakis A, Vrekoussis T, Zoumakis E, Navrozoglou I, Kalantaridou SN (2018) CRH receptors in human reproduction. Curr Mol Pharmacol 11:81–87. https://doi.org/10.2174/1874467210666170224094146
Man AWC, Zhou Y, Lam UDP, Reifenberg G, Werner A, Habermeier A, Closs EI, Daiber A, Münzel T, Xia N, Li H (2022) L-Citrulline ameliorates pathophysiology in a rat model of superimposed preeclampsia. Br J Pharmacol 179:3007–3023. https://doi.org/10.1111/bph.15783
Mannaerts D, Faes E, Goovaerts I, Stoop T, Cornette J, Gyselaers W, Spaanderman M, Van Craenenbroeck EM, Jacquemyn Y (2017) Flow-mediated dilation and peripheral arterial tonometry are disturbed in preeclampsia and reflect different aspects of endothelial function. Am J Phys Regul Integr Comp Phys 313:R518–R525. https://doi.org/10.1152/ajpregu.00514.2016
Matsushima S, Shimizu A, Kondo M, Asano H, Ueno N, Nakayama H, Sato N, Komeno M, Ogita H, Kurokawa-Seo M (2020) Anosmin-1 activates vascular endothelial growth factor receptor and its related signaling pathway for olfactory bulb angiogenesis. Sci Rep 10:188. https://doi.org/10.1038/s41598-019-57040-3
Maynard SE, Min J-Y, Merchan J, Lim K-H, Li J, Mondal S, Libermann TA, Morgan JP, Sellke FW, Stillman IE, Epstein FH, Sukhatme VP, Karumanchi SA (2003) Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 111:649–658. https://doi.org/10.1172/JCI17189
Mehta S, Stewart DJ, Levy RD (1996) The hypotensive effect of L-arginine is associated with increased expired nitric oxide in humans. Chest 109:1550–1555. https://doi.org/10.1378/chest.109.6.1550
Milman N, Paszkowski T, Cetin I, Castelo-Branco C (2016) Supplementation during pregnancy: beliefs and science. Gynecol Endocrinol 32:509–516. https://doi.org/10.3109/09513590.2016.1149161
Montfort WR, Wales JA, Weichsel A (2017) Structure and activation of soluble guanylyl cyclase, the nitric oxide sensor. Antioxid Redox Signal 26:107–121. https://doi.org/10.1089/ars.2016.6693
Morita M, Hayashi T, Ochiai M, Maeda M, Yamaguchi T, Ina K, Kuzuya M (2014) Oral supplementation with a combination of l-citrulline and l-arginine rapidly increases plasma l-arginine concentration and enhances NO bioavailability. Biochem Biophys Res Commun 454:53–57. https://doi.org/10.1016/j.bbrc.2014.10.029
Moura JRSA de, Sass N, Guimarães SB, Vasconcelos PRL de, Mattar R, Kulay L (2006) Effects of L-arginine oral supplements in pregnant spontaneously hypertensive rats. Acta Cir Bras 21:192–196. https://doi.org/10.1590/s0102-86502006000400001
Mullershausen F, Friebe A, Feil R, Thompson WJ, Hofmann F, Koesling D (2003) Direct activation of PDE5 by cGMP: long-term effects within NO/cGMP signaling. J Cell Biol 160:719–727. https://doi.org/10.1083/jcb.200211041
Murphy SR, LaMarca BBD, Cockrell K, Granger JP (2010) Role of endothelin in mediating soluble fms-like tyrosine kinase 1-induced hypertension in pregnant rats. Hypertens Dallas Tex 1979(55):394–398. https://doi.org/10.1161/HYPERTENSIONAHA.109.141473
Murphy SR, LaMarca B, Cockrell K, Arany M, Granger JP (2012) L-arginine supplementation abolishes the blood pressure and endothelin response to chronic increases in plasma sFlt-1 in pregnant rats. Am J Phys Regul Integr Comp Phys 302:R259–R263. https://doi.org/10.1152/ajpregu.00319.2011
Nema J, Sundrani D, Joshi S (2020) Prenatal vitamin D supplementation reduces blood pressure and improves placental angiogenesis in an animal model of preeclampsia. Food Funct 11:10413–10422. https://doi.org/10.1039/d0fo01782e
Neri I, Monari F, Sgarbi L, Berardi A, Masellis G, Facchinetti F (2010) L-arginine supplementation in women with chronic hypertension: impact on blood pressure and maternal and neonatal complications. J Matern Fetal Neonatal Med 23:1456–1460. https://doi.org/10.3109/14767051003677962
Nishizawa H, Pryor-Koishi K, Suzuki M, Kato T, Sekiya T, Tada S, Kurahashi H, Udagawa Y (2009) Analysis of nitric oxide metabolism as a placental or maternal factor underlying the etiology of pre-eclampsia. Gynecol Obstet Investig 68:239–247. https://doi.org/10.1159/000238381
Noris M, Perico N, Remuzzi G (2005) Mechanisms of disease: pre-eclampsia. Nat Clin Pract Nephrol 1:98–114.; quiz 120. https://doi.org/10.1038/ncpneph0035
Novakovic B, Evain-Brion D, Murthi P, Fournier T, Saffery R (2017) Variable DAXX gene methylation is a common feature of placental trophoblast differentiation, preeclampsia, and response to hypoxia. FASEB J 31:2380–2392. https://doi.org/10.1096/fj.201601189RR
Novembri R, De Clemente C, Funghi L, Torricelli M, Voltolini C, Challis JR, Petraglia F (2015) Corticotropin releasing hormone and Urocortin 2 activate inflammatory pathways in cultured trophoblast cell lines. Eur J Obstet Gynecol Reprod Biol 195:200–205. https://doi.org/10.1016/j.ejogrb.2015.10.027
Ognibene DT, Moss MB, Matsuura C, Brunini TM, de Moura RS, Mendes-Ribeiro AC, Resende AdeC (2010) Characterization of the L-arginine-NO-cGMP pathway in spontaneously hypertensive rat platelets: the effects of pregnancy. Hypertens Res 33:899–904. https://doi.org/10.1038/hr.2010.102
Oludare GO, Jinadu HD, Aro OO (2018) L-arginine attenuates blood pressure and reverses the suppression of angiogenic risk factors in a rat model of preeclampsia. Pathophysiology 25:389–395. https://doi.org/10.1016/j.pathophys.2018.08.001
Papapetropoulos A, García-Cardeña G, Madri JA, Sessa WC (1997) Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest 100:3131–3139. https://doi.org/10.1172/JCI119868
Parchem JG, Kanasaki K, Kanasaki M, Sugimoto H, Xie L, Hamano Y, Lee SB, Gattone VH, Parry S, Strauss JF, Garovic VD, McElrath TF, Lu KH, Sibai BM, LeBleu VS, Carmeliet P, Kalluri R (2018) Loss of placental growth factor ameliorates maternal hypertension and preeclampsia in mice. J Clin Invest 128:5008–5017. https://doi.org/10.1172/JCI99026
Pilz S, Zittermann A, Obeid R, Hahn A, Pludowski P, Trummer C, Lerchbaum E, Pérez-López FR, Karras SN, März W (2018) The role of vitamin D in fertility and during pregnancy and lactation: a review of clinical data. Int J Environ Res Public Health 15:E2241. https://doi.org/10.3390/ijerph15102241
Poniedziałek-Czajkowska E, Marciniak B, Kimber-Trojnar Z, Leszczyńska-Gorzelak B, Oleszczuk J (2011) Nitric oxide in normal and preeclamptic pregnancy. Curr Pharm Biotechnol 12:743–749. https://doi.org/10.2174/138920111795470921
Rahimi R, Nikfar S, Rezaie A, Abdollahi M (2009) A meta-analysis on the efficacy and safety of combined vitamin C and E supplementation in preeclamptic women. Hypertens Pregnancy 28:417–434. https://doi.org/10.3109/10641950802629667
Rana S, Lemoine E, Granger JP, Karumanchi SA (2019) Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res 124:1094–1112. https://doi.org/10.1161/CIRCRESAHA.118.313276
Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy (2000) Am J Obstet Gynecol 183:S1–S22
Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK (1989) Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol 161:1200–1204. https://doi.org/10.1016/0002-9378(89)90665-0
Rojas S, Basualto E, Valdivia L, Vallejos N, Ceballos K, Peña E, Rivas C, Nualart F, Guzmán-Gutiérrez E, Escudero C, Toledo F, Sobrevia L, Cid M, González M (2020) The activity of IKCa and BKCa channels contributes to insulin-mediated NO synthesis and vascular tone regulation in human umbilical vein. Nitric Oxide Biol Chem 99:7–16. https://doi.org/10.1016/j.niox.2020.03.004
Roman CD, Choy H, Nanney L, Riordan C, Parman K, Johnson D, Beauchamp RD (2002) Vascular endothelial growth factor-mediated angiogenesis inhibition and postoperative wound healing in rats. J Surg Res 105:43–47. https://doi.org/10.1006/jsre.2002.6444
Romero R, Nien JK, Espinoza J, Todem D, Fu W, Chung H, Kusanovic JP, Gotsch F, Erez O, Mazaki-Tovi S, Gomez R, Edwin S, Chaiworapongsa T, Levine RJ, Karumanchi SA (2008) A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. J Matern Fetal Neonatal Med 21:9–23. https://doi.org/10.1080/14767050701830480
Rytlewski K, Olszanecki R, Korbut R, Zdebski Z (2005) Effects of prolonged oral supplementation with l-arginine on blood pressure and nitric oxide synthesis in preeclampsia. Eur J Clin Investig 35:32–37. https://doi.org/10.1111/j.1365-2362.2005.01445.x
Rytlewski K, Olszanecki R, Lauterbach R, Grzyb A, Basta A (2006) Effects of oral L-arginine on the foetal condition and neonatal outcome in preeclampsia: a preliminary report. Basic Clin Pharmacol Toxicol 99:146–152. https://doi.org/10.1111/j.1742-7843.2006.pto_468.x
Sandrim VC, Palei ACT, Metzger IF, Gomes VA, Cavalli RC, Tanus-Santos JE (2008) Nitric oxide formation is inversely related to serum levels of antiangiogenic factors soluble fms-like tyrosine kinase-1 and soluble endogline in preeclampsia. Hypertens Dallas Tex 1979(52):402–407. https://doi.org/10.1161/HYPERTENSIONAHA.108.115006
Say L, Chou D, Gemmill A, Tunçalp Ö, Moller A-B, Daniels J, Gülmezoglu AM, Temmerman M, Alkema L (2014) Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health 2:e323–e333. https://doi.org/10.1016/S2214-109X(14)70227-X
Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, Spickler W, Schulze F, Böger RH (2008) Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol 65:51–59. https://doi.org/10.1111/j.1365-2125.2007.02990.x
Seçilmiş MA, Ozü OY, Emre M, Büyükafşar K, Kiroglu OE, Ertuğ P, Karataş Y, Onder S, Singirik E (2007) Urocortin induces endothelium-dependent vasodilatation and hyperpolarization of rat mesenteric arteries by activating Ca2+−activated K+ channels. Tohoku J Exp Med 213:89–98. https://doi.org/10.1620/tjem.213.89
Serrano-Díaz NC, Gamboa-Delgado EM, Domínguez-Urrego CL, Vesga-Varela AL, Serrano-Gómez SE, Quintero-Lesmes DC (2018) Vitamin D and risk of preeclampsia: a systematic review and meta-analysis. Biomed Rev Inst Nac Salud 38(Suppl 1):43–53. https://doi.org/10.7705/biomedica.v38i0.3683
Shin S, Mohan S, Fung H-L (2011) Intracellular l-arginine concentration does not determine NO production in endothelial cells: implications on the “l-arginine paradox”. Biochem Biophys Res Commun 414:660–663. https://doi.org/10.1016/j.bbrc.2011.09.112
Shinya T, Yokota T, Nakayama S, Oki S, Mutoh J, Takahashi S, Sato K (2015) Orally administered mucolytic drug L-Carbocisteine inhibits angiogenesis and tumor growth in mice. J Pharmacol Exp Ther 354:269–278. https://doi.org/10.1124/jpet.115.224816
Sovio U, Gaccioli F, Cook E, Hund M, Charnock-Jones DS, Smith GCS (2017) Prediction of preeclampsia using the soluble fms-like tyrosine kinase 1 to placental growth factor ratio: a prospective cohort study of unselected nulliparous women. Hypertens Dallas Tex 1979(69):731–738. https://doi.org/10.1161/HYPERTENSIONAHA.116.08620
Speake PF, Glazier JD, Ayuk PT-Y, Reade M, Sibley CP, D’Souza SW (2003) L-Arginine transport across the basal plasma membrane of the syncytiotrophoblast of the human placenta from normal and preeclamptic pregnancies. J Clin Endocrinol Metab 88:4287–4292. https://doi.org/10.1210/jc.2003-030067
Staff AC (2019) The two-stage placental model of preeclampsia: an update. J Reprod Immunol 134–135:1–10. https://doi.org/10.1016/j.jri.2019.07.004
Staff AC, Berge L, Haugen G, Lorentzen B, Mikkelsen B, Henriksen T (2004) Dietary supplementation with L-arginine or placebo in women with pre-eclampsia. Acta Obstet Gynecol Scand 83:103–107
Staff AC, Benton SJ, von Dadelszen P, Roberts JM, Taylor RN, Powers RW, Charnock-Jones DS, Redman CWG (2013) Redefining preeclampsia using placenta-derived biomarkers. Hypertens Dallas Tex 1979(61):932–942. https://doi.org/10.1161/HYPERTENSIONAHA.111.00250
Staff AC, Johnsen GM, Dechend R, Redman CWG (2014) Preeclampsia and uteroplacental acute atherosis: immune and inflammatory factors. J Reprod Immunol 101–102:120–126. https://doi.org/10.1016/j.jri.2013.09.001
Suschek CV, Schnorr O, Hemmrich K, Aust O, Klotz L-O, Sies H, Kolb-Bachofen V (2003) Critical role of L-arginine in endothelial cell survival during oxidative stress. Circulation 107:2607–2614. https://doi.org/10.1161/01.CIR.0000066909.13953.F1
Tam Tam KB, Lamarca B, Arany M, Cockrell K, Fournier L, Murphy S, Martin JN, Granger JP (2011) Role of reactive oxygen species during hypertension in response to chronic antiangiogenic factor (sFlt-1) excess in pregnant rats. Am J Hypertens 24:110–113. https://doi.org/10.1038/ajh.2010.180
Tashie W, Fondjo LA, Owiredu WKBA, Ephraim RKD, Asare L, Adu-Gyamfi EA, Seidu L (2020) Altered bioavailability of nitric oxide and L-arginine is a key determinant of endothelial dysfunction in preeclampsia. Biomed Res Int 2020. https://doi.org/10.1155/2020/3251956
Tran N-T, Amarger V, Bourdon A, Misbert E, Grit I, Winer N, Darmaun D (2017) Maternal citrulline supplementation enhances placental function and fetal growth in a rat model of IUGR: involvement of insulin-like growth factor 2 and angiogenic factors. J Matern Fetal Neonatal Med 30:1906–1911. https://doi.org/10.1080/14767058.2016.1229768
Tropea T, De Francesco EM, Rigiracciolo D, Maggiolini M, Wareing M, Osol G, Mandalà M (2015) Pregnancy augments G protein estrogen receptor (GPER) induced vasodilation in rat uterine arteries via the nitric oxide – cGMP Signaling pathway. PLoS One 10:e0141997. https://doi.org/10.1371/journal.pone.0141997
Tsatsaris V, Goffin F, Munaut C, Brichant J-F, Pignon M-R, Noel A, Schaaps J-P, Cabrol D, Frankenne F, Foidart J-M (2003) Overexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences. J Clin Endocrinol Metab 88:5555–5563. https://doi.org/10.1210/jc.2003-030528
Vadillo-Ortega F, Perichart-Perera O, Espino S, Avila-Vergara MA, Ibarra I, Ahued R, Godines M, Parry S, Macones G, Strauss JF (2011) 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 342:d2901. https://doi.org/10.1136/bmj.d2901
Vaka VR, McMaster KM, Cunningham MW, Ibrahim T, Hazlewood R, Usry N, Cornelius DC, Amaral LM, LaMarca B (2018) Role of mitochondrial dysfunction and reactive oxygen species in mediating hypertension in the reduced uterine perfusion pressure rat model of preeclampsia. Hypertens Dallas Tex 1979(72):703–711. https://doi.org/10.1161/HYPERTENSIONAHA.118.11290
Valaei K, Mehrabani J, Wong A (2022) Effects of l-citrulline supplementation on nitric oxide and antioxidant markers after high-intensity interval exercise in young men: a randomised controlled trial. Br J Nutr 127:1303–1312. https://doi.org/10.1017/S0007114521002178
Volino-Souza M, de Oliveira GV, Conte-Junior CA, Figueroa A, Alvares TS (2022) Current evidence of watermelon (Citrullus lanatus) ingestion on vascular health: a food science and technology perspective. Nutrients 14:2913. https://doi.org/10.3390/nu14142913
Wang N, Li R, Xue M (2019a) Potential regulatory network in the PSG10P/miR-19a-3p/IL1RAP pathway is possibly involved in preeclampsia pathogenesis. J Cell Mol Med 23:852–864. https://doi.org/10.1111/jcmm.13985
Wang Q, Deng Y, Huang L, Zeng W, Chen S, Lv B, Jiang W, Han Y, Ding H, Wen M, Zeng H (2019b) Hypertonic saline downregulates endothelial cell-derived VEGF expression and reduces blood-brain barrier permeability induced by cerebral ischaemia via the VEGFR2/eNOS pathway. Int J Mol Med 44:1078–1090. https://doi.org/10.3892/ijmm.2019.4262
Weckman AM, McDonald CR, Baxter J-AB, Fawzi WW, Conroy AL, Kain KC (2019) Perspective: L-arginine and L-citrulline supplementation in pregnancy: a potential strategy to improve birth outcomes in low-resource settings. Adv Nutr 10:765–777. https://doi.org/10.1093/advances/nmz015
Weinstein L (2005) Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy. Am J Obstet Gynecol 1982 193:859.; discussion 860. https://doi.org/10.1016/j.ajog.2005.02.113
Wong MK, Li EW, Adam M, Selvaganapathy PR, Raha S (2020) Establishment of an in vitro placental barrier model cultured under physiologically relevant oxygen levels. Mol Hum Reprod 26:353–365. https://doi.org/10.1093/molehr/gaaa018
Wu G, Bazer FW, Cudd TA, Jobgen WS, Kim SW, Lassala A, Li P, Matis JH, Meininger CJ, Spencer TE (2007a) Pharmacokinetics and safety of arginine supplementation in animals. J Nutr 137:1673S–1680S. https://doi.org/10.1093/jn/137.6.1673S
Wu G, Collins JK, Perkins-Veazie P, Siddiq M, Dolan KD, Kelly KA, Heaps CL, Meininger CJ (2007b) Dietary supplementation with watermelon pomace juice enhances arginine availability and ameliorates the metabolic syndrome in Zucker diabetic fatty rats. J Nutr 137:2680–2685. https://doi.org/10.1093/jn/137.12.2680
Xu L, Wang X, Wang C, Li W, Liu H (2022) L-arginine supplementation improved neonatal outcomes in pregnancies with hypertensive disorder or intrauterine growth restriction: a systematic review and meta-analysis of randomized controlled trials. Clin Nutr 41:1512–1522. https://doi.org/10.1016/j.clnu.2022.05.014
Yang Q, Underwood MJ, He G-W (2012) Calcium-activated potassium channels in vasculature in response to ischemia-reperfusion. J Cardiovasc Pharmacol 59:109–115. https://doi.org/10.1097/FJC.0b013e318210fb4b
Yuan J, Wang X, Xie Y, Wang Y, Dong L, Li H, Zhu T (2017) Circulating asymmetric dimethylarginine and the risk of preeclampsia: a meta-analysis based on 1338 participants. Oncotarget 8:43944–43952. https://doi.org/10.18632/oncotarget.16543
Zawiejska A, Wender-Ozegowska E, Iciek R, Brazert J (2014) Concentrations of endothelial nitric oxide synthase, angiotensin-converting enzyme, vascular endothelial growth factor and placental growth factor in maternal blood and maternal metabolic status in pregnancy complicated by hypertensive disorders. J Hum Hypertens 28:670–676. https://doi.org/10.1038/jhh.2014.42
Zeng X, Wang F, Fan X, Yang W, Zhou B, Li P, Yin Y, Wu G, Wang J (2008) Dietary arginine supplementation during early pregnancy enhances embryonic survival in rats. J Nutr 138:1421–1425. https://doi.org/10.1093/jn/138.8.1421
Zeng X, Mao X, Huang Z, Wang F, Wu G, Qiao S (2013) Arginine enhances embryo implantation in rats through PI3K/PKB/mTOR/NO signaling pathway during early pregnancy. Reprod Camb Engl 145:1–7. https://doi.org/10.1530/REP-12-0254
Zhang Y, Zhao H-J, Xia X-R, Diao F-Y, Ma X, Wang J, Gao L, Liu J, Gao C, Cui Y-G, Liu J-Y (2019) Hypoxia-induced and HIF1α-VEGF-mediated tight junction dysfunction in choriocarcinoma cells: implications for preeclampsia. Clin Chim Acta Int J Clin Chem 489:203–211. https://doi.org/10.1016/j.cca.2017.12.010
Zullino S, Buzzella F, Simoncini T (2018) Nitric oxide and the biology of pregnancy. Vasc Pharmacol 110:71–74. https://doi.org/10.1016/j.vph.2018.07.004
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Ortiz-Cerda, T., Mosso, C., Alcudia, A., Vázquez-Román, V., González-Ortiz, M. (2023). Pathophysiology of Preeclampsia and L-Arginine/L-Citrulline Supplementation as a Potential Strategy to Improve Birth Outcomes. In: Gonzalez-Ortiz, M. (eds) Advances in Maternal-Fetal Biomedicine. Advances in Experimental Medicine and Biology, vol 1428. Springer, Cham. https://doi.org/10.1007/978-3-031-32554-0_6
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