Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2021, 165(4):395-401 | DOI: 10.5507/bp.2020.062

Levels of endothelial substances in patients with newly identified hypertension compared with healthy controls

Vladislav Biela, Jan Novaka, b, Veronika Rimalovac, Marie Tomandlovad, Josef Tomandld, Jiri Spaca, Miroslav Souceka
a 2nd Department of Internal Medicine, St. Anne's University Hospital in Brno and Faculty of Medicine, Pekarska 53, Brno, 65691, Czech Republic
b Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, 62500, Czech Republic
c Center of Biostatistics, International Clinical Research Center of St. Anne´s University Hospital, Pekarska 53, Brno, 65691, Czech Republic
d Department of Biochemistry, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, 62500, Czech Republic

Introduction: Endothelial dysfunction occurs at the very beginning of hypertension. The primary goal of our study was to determine plasmatic levels of multiple endothelial substances in otherwise healthy patients with primary hypertension and compare them to healthy individuals. Secondary goals were to determine the change in NOx levels after initiation of treatment and to compare the NOx levels in patients with established resistant hypertension.

Materials and Methods: 87 consecutive patients were enrolled. In the exploratory cohort of 22 healthy and 28 hypertensive individuals, plasmatic levels of big endotelin-1, asymmetric dimethylarginin, osteopontin, oxidized LDL, 3-nitro-L-tyrosine, growth/differentiation factor 15, intercellular adhesion molecule, vascular cell adhesion molecule, tumor necrosis factor-α, vascular endothelial growth factor, interleukins -1β, -6 and nitric oxide levels (NO, expressed as NOx) were determined. The remaining 27 individuals were used as a validation cohort. Ten patients with established resistant hypertension were enrolled from our Hypertension Clinic.

Results: There was a statistically significant difference in NOx levels between healthy controls and hypertensive patients/resistant hypertensive patients: 45.164 µmol/L ± 48.627 vs 17.763 µmol/L ± 10.333 (P=0.00004)/14.36 µmol/L ± 7.194 (P=0.00007).

Conclusion: We identified a decrease in total NOx plasmatic levels in otherwise healthy patients with primary hypertension that was more profound in patients with resistant hypertension. Plasmatic levels of other determined endothelial substances did not differ among the groups. However, due to the significant variability of plasmatic NOx levels even in healthy controls and many factors that affect it, we cannot recommend it to be used to assess endothelial function routinely.

Keywords: hypertension, nitric oxide, plasma, endothelial dysfunction

Received: August 12, 2020; Revised: November 25, 2020; Accepted: December 8, 2020; Prepublished online: January 12, 2021; Published: November 23, 2021  Show citation

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Biel, V., Novak, J., Rimalova, V., Tomandlova, M., Tomandl, J., Spac, J., & Soucek, M. (2021). Levels of endothelial substances in patients with newly identified hypertension compared with healthy controls. Biomedical papers165(4), 395-401. doi: 10.5507/bp.2020.062
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References

  1. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I; Authors/Task Force Members:. 2018 ESC/ESH. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens 2018;36(10):1953-2041. Go to original source... Go to PubMed...
  2. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, Chalmers J, Rodgers A, Rahimi K. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet Lond Engl 2016;387(10022):957-67. Go to original source... Go to PubMed...
  3. Weaver DJ. Hypertension in Children and Adolescents. Pediatr Rev 2017;38(8):369-82. Go to original source... Go to PubMed...
  4. WHO | Raised blood pressure [Internet]. WHO. [cited 2017 Jul 3]. Available on: http://www.who.int/gho/ncd/risk_factors/blood_pressure_prevalence_text/en/
  5. Konukoglu D, Uzun H. Endothelial Dysfunction and Hypertension. Adv Exp Med Biol 2017;956:511-40. Go to original source... Go to PubMed...
  6. Biel V, Novak J, Pluhacek L, Spac J. Flow mediated dilation - její úloha a význam ve screeningu rizika kardiovaskulárních chorob. Internî Med 2019; 21(2): 92-96. (In Czech) Go to original source...
  7. Williams B, Mancia G, Spiering W, Rosei EA, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I, ESC Scientific Document Group 2018 ESC/ESH Guidelines for the management of arterial hypertension Eur Heart J 2018;33:3021-104. Go to original source... Go to PubMed...
  8. Alrefai AA, Habib D, Yassen RI, Gabr MK, Habeeb RM. Association of endothelial nitric oxide synthase (eNOS) gene G894T polymorphism with hypertension risk and complications. Mol Cell Biochem 2016;421(1-2):103-10. Go to original source... Go to PubMed...
  9. Jasperse JL, Laughlin MH. Endothelial function and exercise training: evidence from studies using animal models. Med Sci Sports Exerc 2006;38(3):445-54. Go to original source... Go to PubMed...
  10. Shek EW, Brands MW, Hall JE. Chronic leptin infusion increases arterial pressure. Hypertens Dallas Tex 1979 1998 (1 Pt 2):409-14. Go to original source... Go to PubMed...
  11. Su Y, Han W, Giraldo C, De Li Y, Blockr ER. Effect of cigarette smoke extract on nitric oxide synthase in pulmonary artery endothelial cells. Am J Respir Cell Mol Biol 1998;19(5):819-25. Go to original source... Go to PubMed...
  12. Walther C, Gielsen S, Hambrecht R. The effect of exercise training on endothelial function in cardiovascular disease in humans. Exerc Sport Sci Rev 2004;32(4):129-34. Go to original source... Go to PubMed...
  13. Vogel RA, Corretti MC, Plotnick GD. Effect of a single high-fat meal on endothelial function in healthy subjects. Am J Cardiol 1997;79(3):350-4. Go to original source... Go to PubMed...
  14. Lundberg JO, Carlström M, Larsen FJ, Weitzberg E. Roles of dietary inorganic nitrate in cardiovascular health and disease. Cardiovasc Res 2011;89(3):525-32. Go to original source... Go to PubMed...
  15. Vasdev S, Gill V. The antihypertensive effect of arginine. Int J Angiol 2008;17(1):7-22. Go to original source... Go to PubMed...
  16. Lin HY, Lee YT, Chan YW, Tse G. Animal models for the study of primary and secondary hypertension in humans. Biomed Rep 2016;5(6):653-9. Go to original source... Go to PubMed...
  17. Node K, Kitakaze M, Yoshikawa H, Kosaka H, Hori M. Reduced plasma concentrations of nitrogen oxide in individuals with essential hypertension. Hypertension 1997;30:405-8. Go to original source... Go to PubMed...
  18. Perticone F, Sciacqua A, Maio R, Perticone M, Galiano Leone G, Bruni R, Di Cello S, Pascale A, Talarico G, Greco L, Andreozzi F, Sesti G. Endothelial dysfunction, ADMA and insulin resistance in essential hypertension. Int J Cardiol 2010;142(3):236-41. Go to original source... Go to PubMed...
  19. Ceconi C, Fox KM, Remme WJ, Simoons ML, Bertrand M, Parrinello G, Kluft C, Blann A, Cokkinos D, Ferrari R; EUROPA Investigators; PERTINENT Investigators and the Statistical Committee. ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT. Cardiovasc Res 2007;73(1):237-46. Go to original source... Go to PubMed...
  20. Ito A, Egashira K, Narishige T, Muramatsu K, Takeshita A. Renin-angiotensin system is involved in the mechanism of increased serum asymmetric dimethylarginine in essential hypertension. Jpn Circ J 2001;65(9):775-8. Go to original source... Go to PubMed...
  21. Aladag MA, Turkoz Y, Parlakpinar H, Gul M. Nebivolol attenuates cerebral vasospasm both by increasing endothelial nitric oxide and by decreasing oxidative stress in an experimental subarachnoid haemorrhage. Br J Neurosurg 2017;31(4):439-45. Go to original source... Go to PubMed...
  22. He Y, Si D, Yang C, Ni L, Li B, Ding M, Yang P. The effects of amlodipine and S(-)-amlodipine on vascular endothelial function in patients with hypertension. Am J Hypertens 2014;27(1):27-31. Go to original source... Go to PubMed...
  23. Tzemos N, Lim PO, Macdonald TM. Valsartan Improves Endothelial Dysfunction in Hypertension: A Randomized, Double-Blind Study. Cardiovasc Ther 2009;27(3):151-8. Go to original source... Go to PubMed...
  24. Kruzliak P, Kovacova G, Pechanova O. Therapeutic potential of nitric oxide donors in the prevention and treatment of angiogenesis-inhibitor-induced hypertension. Angiogenesis 2013;16(2):289-95. Go to original source... Go to PubMed...
  25. Rosselli, M, Imthurm B, Macas E, Keller PJ, Dubey RK, Circulating Nitrite/Nitrate Levels Increase with Follicular Development: Indirect Evidence for Estradiol-Mediated NO Release. Biochem Biophys Res Commun 1994;202(3):1543-52. doi: 10.1006/bbrc.1994.2107 Go to original source... Go to PubMed...

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