Vascular Adaptations in Pregnancy: The Critical Role of Endothelial Function and Nitric Oxide in Maternal-Fetal Health

Authors

DOI:

https://doi.org/10.36283/ziun-pjmd14-2/046

Keywords:

Vascular Endothelial Growth Factors , Nitric Oxide, Endothelin-1, Brachial Artery, Hypertension, Pregnancy-Induced Hypertension, Preeclampsia

Abstract

Background: Endothelial dysfunction is a critical factor in hypertensive disorders of pregnancy, such as preeclampsia. This study aimed to evaluate the role of endothelial function, nitric oxide (NO), and endothelin-1 (ET-1) in normotensive and hypertensive pregnancies to understand the underlying vascular adaptations.

Methods: A cross-sectional study was conducted at LUMHS, Jamshoro, from October 2023 to June 2024. A total of 120 pregnant women were divided into normotensive (n=60) and hypertensive (n=60) groups. Participants included pregnant women aged 18 to 40 years with singleton pregnancies between 20 and 36 weeks of gestation. Participants were recruited using a purposive sampling technique from the Obstetrics and Gynecology Department. Serum NO and ET-1 levels were measured, and endothelial function was assessed using flow-mediated dilation (FMD). Data analysis using SPSS 26.0 involved descriptive statistics, independent t-tests for NO and FMD comparisons, chi-square tests for categorical variables, and multivariate regression to adjust for confounders such as maternal age, BMI, and gestational age.

Results: Hypertensive women had lower NO levels (24.98 ± 4.72 vs. 34.23 ± 4.54 µmol/L) and FMD values (6.09 ± 1.55% vs. 10.14 ± 1.49%), and higher ET-1 levels (4.46 ± 0.72 vs. 2.52 ± 0.48 pg/mL) than normotensive women (all p < 0.0001). NO correlated positively with FMD (r = 0.61), while ET-1 correlated negatively with NO (r = -0.55) and FMD (r = -0.69). Multiple regression identified NO and ET-1 as significant FMD predictors.

Conclusion: Endothelial dysfunction in hypertensive pregnancies is characterized by reduced NO levels, elevated ET-1 levels, and impaired FMD.

 

Author Biographies

  • Hina Riaz, Dow University of Health Sciences, Karachi, Pakistan.

    Department of Physiology,

  • Urooj Bhatti, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan

    Department of Physiology,

  • Keenjher Rani, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan

    Department of Physiology,

  • Afsheen Abro, Bilawal Medical College for Boys, Jamshoro,Pakistan.

    Department of Physiology,

  • Rabia Uqaili, Jinnah Sindh Medical University, Karachi,Pakistan.

    Department of Physiology,

  • Rubina Ahmdani, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan

    Department of Physiology,

References

Conrad KP. Emerging role of nitric oxide in regulation of vascular function during pregnancy. Am J Physiol Renal Physiol. 2011;300(2):F251–F262. doi:10.1152/ajprenal.00750.2010

Chun S, Malek AM, Braams R, et al. Nitric oxide and pregnancy: NO synthesis and signaling pathways in vascular adaptation. Physiology (Bethesda). 2020;35(4):260–269. doi:10.1152/physiol.00008.2020

Osol G, Mandala M. Maternal uterine vascular remodeling during pregnancy. Physiology (Bethesda). 2009;24(2):58–71. doi:10.1152/physiol.00033.2008

Sánchez-Aranguren LC, Prada CE, Riaño-Medina CE, Lopez M. Endothelial dysfunction and preeclampsia: role of oxidative stress. Front Physiol. 2018;9:973. doi:10.3389/fphys.2018.00973

Rennie MY, Whiteley KJ, Lysiak JJ, et al. Role of nitric oxide in vascular adaptation during pregnancy. Reprod Sci. 2021;28(1):12–21. doi:10.1007/s43032-020-00245-0

Phipps E, Prasanna D, Brima W, Jim B. Preeclampsia: updates in pathogenesis, definitions, and guidelines. Clin J Am Soc Nephrol. 2016;11(6):1102–1113. doi:10.2215/CJN.12081115

Lu F, Longo M, Tamayo E, et al. The effect of overexpression of endothelial nitric oxide synthase on placental angiogenesis in a mouse model. Am J Physiol Heart Circ Physiol. 2007;293(6):H3036–H3044. doi:10.1152/ajpheart.00677.2007

Mannaerts D, Faes E, Cos P, et al. Endothelial dysfunction in preeclampsia: the role of high-density lipoproteins. J Hypertens. 2018;36(6):1170–1180. doi:10.1097/HJH.0000000000001656

Ayala DE, Ucieda R, Hermida RC. Chronotherapy with low-dose aspirin for prevention of complications in pregnancy. Chronobiol Int. 2013;30(1–2):260–279. doi:10.3109/07420528.2012.719965

Banek CT, Bauer AJ, Gingery A, et al. Endothelial NO synthase uncoupling in placentas from women with preeclampsia. Hypertension. 2012;60(5):1268–1275. doi:10.1161/HYPERTENSIONAHA.112.198853

Roberts JM, Escudero C. The placenta in preeclampsia. Pregnancy Hypertens. 2012;2(2):72–83. doi:10.1016/j.preghy.2012.01.001

Amaral LM, Cornelius DC, Harmon A, et al. Hypertension in pregnancy: a major risk factor for maternal and fetal morbidity and mortality. Am J Hypertens. 2015;28(2):147–158. doi:10.1093/ajh/hpu190

Turbeville HR, Sasser JM. Preeclampsia beyond pregnancy: long-term consequences for mother and child. Am J Physiol Renal Physiol. 2020;318(6):F1315–F1326. doi:10.1152/ajprenal.00016.2020

Spradley FT. Metabolic abnormalities and obesity’s impact on preeclampsia pathogenesis. Am J Physiol Regul Integr Comp Physiol. 2017;312(1):R5–R12. doi:10.1152/ajpregu.00336.2016

Khalil A, Cooper D, Harrington K. Pulse wave analysis: a preliminary study of a novel technique for the prediction of preeclampsia. BJOG. 2009;116(2):268–276. doi:10.1111/j.1471-0528.2008.01949.x

Staff AC, Redman CW, Williams D, et al. Pregnancy and long-term maternal cardiovascular health: progress through harmonization and consortium research. Hypertension. 2016;67(2):251–260. doi:10.1161/HYPERTENSIONAHA.115.06767

Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350(7):672–683. doi:10.1056/NEJMoa031884

George EM, Granger JP. Endothelin: key mediator of hypertension in preeclampsia. Am J Hypertens. 2011;24(9):964–969. doi:10.1038/ajh.2011.132

Shah DM. The role of RAS in the pathogenesis of preeclampsia. Curr Hypertens Rep. 2006;8(2):144–152. doi:10.1007/s11906-006-0004-8

Gupta S, Agarwal A, Banerjee J, et al. Oxidative stress and its role in female infertility and assisted reproduction: clinical implications. Reprod Biomed Online. 2007;11(5):641–650. doi:10.1016/S1472-6483(10)60679-1

Sgambati E, Marini M, Zappolini A, et al. Vascular endothelial growth factor expression in the placentas of pregnancies complicated by hypertension. J Clin Pathol. 2004;57(5):470–475. doi:10.1136/jcp.2003.013433

Huppertz B. Placental origins of preeclampsia: challenging the current hypothesis. Hypertension. 2008;51(4):970–975. doi:10.1161/HYPERTENSIONAHA.107.107607

Lu X, Wang L, Lin C, et al. Endothelin-1 and endothelial dysfunction in pregnancy-induced hypertension. J Hum Hypertens. 2020;34(5):351–357. doi:10.1038/s41371-019-0278-6

Brownfoot FC, Tong S, Hannan NJ, et al. Endothelin and endothelin antagonists in preeclampsia. Clin Sci (Lond). 2017;131(6):441–448. doi:10.1042/CS20160778

Ahmed A, Ramma W. Unravelling the theories of preeclampsia: are the protective pathways the new paradigm? Br J Pharmacol. 2015;172(6):1574–1586. doi:10.1111/bph.12966

Downloads

Published

2025-04-13

How to Cite

1.
Riaz H, Bhatti U, Rani K, Abro A, Uqaili R, Ahmdani R. Vascular Adaptations in Pregnancy: The Critical Role of Endothelial Function and Nitric Oxide in Maternal-Fetal Health. PJMD [Internet]. 2025 Apr. 13 [cited 2025 Jul. 10];14(2):301-7. Available from: https://ojs.zu.edu.pk/pjmd/article/view/3620

Similar Articles

1-10 of 326

You may also start an advanced similarity search for this article.