Markers of Endothelial Dysfunction as Criteria for Differential Diagnosis of Hypertensive Disorders in Pregnant Women

The aim of the investigation was tostudy indicators of microvasculature oxygenation and markers of endothelial dysfunction in the peripheral blood of pregnant women with various hypertensive disorders and on the basis of the resulting findings to suggest new diagnostic criteria for this pathology.

Materials and Methods. The study involved 153 women at 22–37 weeks gestation: 41 women with chronic arterial hypertension (CAH), 22 women with CAH and secondary preeclampsia (PE), 50 women with PE, 40 women with normal blood pressure. The level of tissue oxygenation (SO₂) was estimated by test with ischemia/reperfusion (Spectrotest, Russia). Desquamated endotheliocytes (DE), total nitrates and nitrites (NOx) were determined in the peripheral blood.

Results. All kinds of hypertensive disorders in pregnant women are accompanied by the development of endothelial dysfunction as evidenced by the change in the level of tissue oxygenation, increase in DE and NOx content in the blood. The extent of endothelial function impairment depends on PE severity.

Conclusion. Changes in endothelium-dependent vascular response found as the result of test with ischemia/reperfusion and the content of venous endothelial cells in pregnant women with hypertensive disorders may serve as diagnostic criteria of hypertensive disorders in pregnancy, giving the possibility to choose tactics of patient management and to start well-timed adequate therapy.

1. World Health Organization. Mirovaya statistika zdravookhraneniya 2013 [World health statistics 2013], http://www.who.int/gho/publications/world_health_statistics/2013/ru/.
2. Russian Federation Ministry of Health. Osnovnye pokazateli zdorov’ya materi i rebenka, deyatel’nost’ sluzhby okhrany detstva i rodovspomozheniya v Rossiyskoy Federatsii [Main indices of mother and child health, work of child welfare and marternity obstetric services in the Russian Federation]. Moscow; 2013.
3. Shekhtman M.M. Rukovodstvo po ekstragenital’noy patologii u beremennykh [Guide for extragenital pathology in pregnant women]. Moscow: Triada-Kh; 1999; 814 p.
4. Panova I.A. Immunnye mekhanizmy razvitiya gestoza u beremennykh zhenshchin. Avtoref. dis. ... dokt. med. nauk [Immune mechanisms of the development of gestosis in pregnant women. DSc Thesis]. Moscow; 2007.
5. Panova I.A., Malyshkina A.I., Kudryashova A.V., Khlipunova D.A., Rockatanskaya E.A., Sytova L.A. Synthesis of the matrix metalloproteinases and its inhibitors by peripheral blood phagocytes of women with hypertansion disorders. Zhurnal akusherstva i zhenskikh bolezney 2015; 64(3): 26–32.
6. Serov V.N. Neotlozhnye sostoyaniya v akusherstve [Emergency conditions in obstetrics]. M: GEOTAR-Media; 2011; 784 s.
7. Bova A.A. The role of endothelial dysfunction in the pathogenesis of arterial hypertension. Meditsinskie novosti 2001; 1: 25–29.
8. Kulakov V.I. Anesteziya i reanimatsiya v akusherstve i ginekologii [Anaesthesia and intensive care in obstetrics and gynecology]. Moscow: Triada-Kh; 2000; 383 p.
9. Chicherina E.N., Padyganova A.V. The structural and functional characteristics of the cardiovascular system and kidneys in pregnant women with chronic arterial hypertension in the presence and absence of obesity. Rossiiskii vestnik akushera-ginekologa 2012; 1: 48–52.
10. Spaan J.J., Ekhart T., Spaanderman M.E., Peeters L.L. Remote hemodynamics and renal function in formerly preeclamptic women. Obstet Gynecol 2009; 113(4): 853–859, http://dx.doi.org/10.1097/AOG.0b013e31819caf0f.
11. Buhimschi C.S., Norwitz E.R., Funai E., Richman S., Guller S., Lockwood C.J., Buhimschi I.A. Urinary angiogenic factors cluster hypertensive disorders and identify women with severe preeclampsia. Am J Obstet Gynecol 2005; 192(3): 734–741, http://dx.doi.org/10.1016/j.ajog.2004.12.052.
12. Logutova L.S., Rad’kov O.V., Kalinkin M.N., Zavarin V.V. The circulation of fetal extracellular deoxyribonucleic acid in the plasma of pregnant women and the formation of clinical and pathogenetic features of arterial hypertension in them. Rossiiskii vestnik akushera-ginekologa 2012; 2: 18–21.
13. Sidorova I.S., Nikitina N.A., Unanyan A.L., Rzayeva A.A., Kinyakin V.V. Pathogenetic rationale for a differentiated approach to managing pregnant women with arterial hypertension and preeclampsia. Akusherstvo i ginekologiya 2013; 2: 35–40.
14. Panova I.A., Kudryashova A.V., Malyshkina A.I., Khlipunova D.A., Rokotyanskaya E.A. Cell adhesion molecule expression by phagocytes as a criterion for the differential diagnosis of hypertensive disorders in pregnant women. Akusherstvo i ginekologiya 2015; 7: 33–37.
15. Panova I.A., Malyshkina A.I., Khlipunova D.A., Rokоtyanskаya E.A., Sytova L.A., Kudryashova A.V. Immunological criteria for differential diagnosis of hypertension in pregnant women. Sovremennye tehnologii v medicine 2015; 7(3): 103–108, http://dx.doi.org/10.17691/stm2015.7.3.15.
16. Kulikov S.A., Posiseeva L.V., Nazarov S.B., Sitnikova O.G., Klycheva M.M. State of nitrergic mechanisms of regulation of the function of the endothelium in pregnant women with severe gestosis. Vrach-aspirant 2011; 3.4(46): 617–621.
17. Hu D., Cai D., Rangan A.V. Blood vessel adaptation with fluctuations in capillary flow distribution. PLoS One 2012; 7(9): e45444, http://dx.doi.org/10.1371/journal.pone.0045444.
18. Savvidou M.D., Hingorani A.D., Tsikas D., Frölich J.C., Vallance P., Nicolaides K.H. Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre-eclampsia. Lancet 2003; 361(9368): 1511–1517, http://dx.doi.org/10.1016/s0140-6736(03)13177-7.
19. Prochazka M., Procházková J., Lubušký M., Pilka R., Úlehlová J., Michalec I., Polák P., Kacerovský M., Slavik L. Markers of endothelial activation in preeclampsia. Clin Lab 2015; 61(1–2): 39–46.
20. Perfilova V.N., Mikhailova L.M., Tyurenkov I.N. Role of endothelial biologically active substances in the prediction of preeclampsia and in the evaluation of its severity. Akusherstvo i ginekologiya 2013; 11: 24–29.
21. Ferlito S. Physiological, metabolic, neuroendocrine and pharmacological regulation of nitric oxide in humans. Minerva Cardioangiol 2000; 48(6): 169–176.
22. Pimentel A.M., Pereira N.R., Costa C.A., Mann G.E., Cordeiro V.S., de Moura R.S., Brunini T.M., Mendes-Ribeiro A.C., Resende A.C. L-arginine-nitric oxide pathway and oxidative stress in plasma and platelets of patients with pre-eclampsia. Hypertens Res 2013; 36(9): 783–788, http://dx.doi.org/10.1038/hr.2013.34.
23. Laskowska M., Laskowska K., Oleszczuk J. The relation of maternal serum eNOS, NOSTRIN and ADMA levels with aetiopathogenesis of preeclampsia and/or intrauterine fetal growth restriction. J Matern Fetal Neonatal 2014; 28(1): 26–32, http://dx.doi.org/10.3109/14767058.2014.900036.

Rokotyanskaya E.A., Malyshkina A.I., Nazarov S.B., Smirnova E.V., Sytova L.A., Panova I.A. Markers of Endothelial Dysfunction as Criteria for Differential Diagnosis of Hypertensive Disorders in Pregnant Women. Sovremennye tehnologii v medicine 2016; 8(3): 75, https://doi.org/10.17691/stm2016.8.3.08