Relationship between the expression of angiotensin II receptors type 1 and vasoactive regulators in arterial hypertension

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Abstract


In the pathogenesis of arterial hypertension (AH), the renin-angiotensin-aldosterone system plays a key role in helping to maintain elevated blood pressure. At the same time, the state of angiotensin-II production (AT II) and the expression level of its receptors on target cells determine the formation of most of the effects underlying the pathogenesis of associated clinical conditions in such patients. Thus, the study of the pathogenesis of AH, namely the study of the role of the AT II axis, the AT II receptor, is an actual scientific and practical task.

Aim. Given the important role of type 1 receptors for AT II in the formation of pathological changes in arterial hypertension, the purpose of this study was to study the peculiarities of the effect of their expression on biochemical processes in patients with arterial hypertension.

Material and methods. In the course of the clinical study, 60 patients of both sexes with hypertension aged 45 to 55 years old were admitted to the clinic for planned treatment. Depending on the initial level of expression of receptors for AT II (AT1R), determined by the serum concentration of the soluble form of type 1 receptors for AT II, the patients were divided into two subgroups with conditionally low (corresponding to the concentration of the soluble form of the receptor for AT II 0.66 ng/ml) and conditionally high (1.57 ng/ml) expression. The analysis showed that high expression of AT1R is associated with elevated plasma levels of renin by 30.8% (p=0.0005), AT II by 48.1% (p=0.00001), E-selectin by 47.9% (p=0.0001), VCAM-1 by 29.1% (p=0.00001), ICAM-1 by 52.9% (p=0.00001), VE-cadherin by 50.9% (p=0.00001), endothelin-1 by 48.8% (p=0.0005), an ACE inhibitor by 13.6% (p=0.047), and CRP by 74.1% (p=0.00002 ) and endoperoxide by 29.7% (p=0.009). Against this background, there was a decrease in the level of apoA1 by 21.6% (p=0.027), ACE by 20.1% (p=0.1), the level of antioxidants by 22.3% (p=0.00001). The analysis showed that in the group with initially high expression of AT1R, there was an increased blood pressure, the level of which, on average, exceeded the values of patients with low expression of the indicated receptor by 24.5 mm Hg (p=0.011). Against the background of therapy in the group with high expression of AT1R, plasma renin activity decreased by 20.3% (p=0.013), endoperoxide by 8.4% (p=0.038), an ACE inhibitor by 14.6% (p=0.02). At the same time, the level of apoA1 increased by 8.5% (p=0.036), antioxidants by 8.6% (p=0.036), ICAM-1 by 5.3% (p=0.05), VE-cadherin by 2.5% (p=0.07). The level of the remaining factors was not statistically significant. In the subgroup with low expression of the AT II receptor, during treatment, there was a decrease in endoperoxide by 12.8% (p=0.031), an ACE inhibitor by 5.5% (p=0.044) without significant changes in other indicators.

Conclusion. In hypertensive patients, higher expression of AT1R is associated with high activation of immune-inflammatory mechanisms, dyslipidemia, an imbalance of the lipid peroxidation system and antioxidant protection, as well as higher renin-angiotensin-aldosterone system activity and increased arterial pressure. On the background of antihypertensive therapy, partial compensation of the identified changes is achieved, including a moderate increase in the level of antioxidants, a decrease in the concentration of endoperoxide, renin activity and an increase in the level of apoA1, while maintaining an increased level of AT II, high expression of receptors to it. These changes indicate the need for further search for effective antihypertensive therapy strategies aimed at limiting the activity of renin-angiotensin-aldosterone system in patients with hypertension.


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About the authors

Anna V. Logatkina

Tula State University

Author for correspondence.
Email: Logatkina_a@mail.ru
ORCID iD: 0000-0002-3397-136X

Russian Federation

Graduate Student

Viktor S. Nikiforov

Mechnikov North-Western State Medical University

Email: viktor.nikiforov@szgmu.ru
ORCID iD: 0000-0001-7862-0937

Russian Federation

D. Sci. (Med.), Prof.

Stanislav S. Bondar'

Tula State University

Email: stos34@mail.ru
ORCID iD: 0000-0003-2749-8366

Russian Federation

Graduate Student

Igor' V. Terekhov

Tula State University

Email: trft@mail.ru
ORCID iD: 0000-0002-6548-083X

Russian Federation

Graduate Student

Vladimir K. Parfeniuk

Saratov State Medical University named after V. I. Razumovsky

Email: parfenyk0111@mail.ru

Russian Federation

D. Sci. (Med.), Prof.

References

  1. ESH/ESC Guidelines for the management of arterial hypertension. J Hypertens 2013; 31: 1281–357. DOI: 10.1201/ b17072-61
  2. Konukoglu D, Uzun H. Endothelial Dysfunction and Hypertension. Adv Exp Med Biol 2017; 956: 511–40. doi: 10.1007/5584_2016_90
  3. Forrester SJ, Booz GW, Sigmund CD et al. Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology. Physiol Rev 2018; 98 (3): 1627–738. doi: 10.1152/physrev.00038.2017
  4. Kawai T, Forrester SJ, O’Brien S et al. AT1 receptor signaling pathways in the cardiovascular system. Pharmacol Res 2017; 125 (Pt A): 4–13. doi: 10.1016/j.phrs.2017.05.008
  5. Бабенко А.Ю., Матвеев Г.А., Алексеенко Т.И. и др. Взаимосвязи компонентов метаболического синдрома с уровнем гормонов, вовлеченных в регуляцию метаболизма жировой ткани. Артериальная гипертензия. 2019; 25 (6): 639–52. doi: 10.18705/1607-419X-2019-25-6-639-652 [Babenko A.Y., Matveev G.A., Alekseenko T.I. et al. Interrelations of components of metabolic syndrome with the level of the hormones involved in regulation of adipose tissue metabolism. Arterialnaya gipertenziya. 2019; 25 (6): 639–52. doi: 10.18705/1607-419X-2019-25-6-639-652 (in Russian).]
  6. Сысоев К.А. Морфофункциональные изменения эндотелия в патогенезе гипертонической болезни. Артериальная гипертензия. 2017; 23 (5): 447–56. doi: 10.18705/1607-419X-2017-23-5-447-456 [Sysoev K.A. Morphofunctional changes of the endothelium in the pathogenesis of hypertension. Arterialnaya gipertenziya. 2017; 23 (5): 447–56. doi: 10.18705/1607-419X-2017-23-5-447-456 (in Russian).]
  7. Севостьянова Е.В., Николаев Ю.А., Митрофанов И.М., Поляков В.Я. Особенности полиморбидности у больных артериальной гипертензией. Артериальная гипертензия. 2019; 25 (2): 200–8. doi: 10.18705/1607-419X-2019-25-2-200-208 [Sevostyanova E.V., Nikolaev Y.A., Mitrofanov I.M., Polyakov V.Y. Polymorbidity in hypertensive patients. Arterialnaya gipertenziya. 2019; 25 (2): 200–8. doi: 10.18705/1607-419X-2019-25-2-200-208 (in Russian).]
  8. Логаткина А.В., Никифоров В.С., Бондарь С.С., Терехов И.В. Воспалительные цитокины и сигнальные системы мононуклеарных клеток периферической крови при ишемической болезни сердца. Клиническая медицина. 2017; 95 (3): 238–44. doi: 10.18821/0023-2149-2017-95-3-238-244 [Logatkina A.V., Nikiforov V.S., Bondar S.S., Terekhov I.V. Inflammatory cytokines and signaling systems of peripheral blood mononuclear cells in coronary heart disease. Klinicheskaya medicina. 2017; 95 (3): 238–4. doi: 10.18821/0023-2149-2017-95-3-238-244 (in Russian).]
  9. Flemming S, Burkard N, Renschler M et al. Soluble VE-cadherin is involved in endothelial barrier breakdown in systemic inflammation and sepsis. Cardiovasc Res 2015; 107 (1): 32–44. doi: 10.1093/cvr/cvv144
  10. Zhang P, Mende U. Functional role, mechanisms of regulation, and therapeutic potential of regulator of G protein signaling 2 in the heart. Trends Cardiovasc Med 2014; 24 (2): 85–93. doi: 10.1016/j.tcm.2013.07.002.
  11. Small HY, Migliarino S, Czesnikiewicz-Guzik M, Guzik T. Hypertension: Focus on autoimmunity and oxidative stress. Free Radic Biol Med 2018; 125: 104–15. doi: 10.1016/j.freeradbiomed.2018.05.085
  12. Liao Z, Cai H, Xu Z et al. Protective Role of Antioxidant Huskless Barley Extracts on TNF-α-Induced Endothelial Dysfunction in Human Vascular Endothelial Cells. Oxid Med Cell Longev 2018; 2018: 3846029. doi: 10.1155/2018/3846029
  13. Le TH, Coffman TM. RGS2: a “turn-off” in hypertension. Journal of Clinical Investigation 2003; 111: 441–3.
  14. Zhang TL, Fu JL, Geng Z et al. The neuroprotective effect of losartan through inhibiting AT1/ASK1/MKK4/JNK3 pathway following cerebral I/R in rat hippocampal CA1 region. CNS Neurosci Ther 2012; 18 (12): 981–7. doi: 10.1111/cns.12015
  15. Roberts E, Ludman AJ, Dworzynski K. The diagnostic accuracy of the natriuretic peptides in heart failure: systematic review and diagnostic meta-analysis in the acute care setting. BMJ 2015; 350: h910. doi: 10.1136/bmj.h910
  16. Tchalla A, Wellenius GA, Boyer S et al. High levels of an endothelial dysfunction marker (sVCAM-1) are associated with injurious and recurrent falls and mortality over a 5-year interval in an older population. Exp Gerontol 2018; 106: 1–7. doi: 10.1016/j.exger.2018.02.020
  17. Alfieri A, Ong AC, Kammerer RA et al. Angiopoietin-1 regulates microvascular reactivity and protects the microcirculation during acute endothelial dysfunction: role of eNOS and VE-cadherin. Pharmacol Res 2014; 80: 43–51. doi: 10.1016/j.phrs.2013.12.008
  18. Бондарь С.С., Терехов И.В., Парфенюк В.К. Содержание в мононуклеарных клетках периферической крови у больных внебольничной пневмонией компонентов G-белков под влиянием низкоинтенсивных микроволн частотой 1 ГГц. Вестник новых медицинских технологий. 2017; 24 (2): 95–104. [Bondar S.S., Terekhov I.V., Parfenyuk V.K. The content of peripheral blood mononuclear cells in patients with community-acquired pneumonia of the components of G-proteins under the influence of low-intensity microwaves at 1 GHz. Vestnik novyh medicinskih tekhnologij. 2017; 24 (2): 95–104 (in Russian).]
  19. Logatkina AV, Bondar SS, Terekhov IV, Nikiforov VS. Correction of Immunoendocrine Disorders in Patients with Ischemic Heart Disease Using Low-intensity Microwave Therapy. Biomedical Engineering. 2017; 51 (2): 133–7. doi: 10.1007/s10527-017-9700-0
  20. Терехов И.В., Никифоров В.С., Бондарь С.С. Изменение содержания компонентов IL/TOLL-сигнального пути и NF-kB в мононуклеарных клетках цельной крови под влиянием низкоинтенсивного электромагнитного излучения частотой 1 ГГц. Гены и клетки. 2017; 12 (2): 90–6. doi: 10.23868/201707020 [Terekhov I.V., Nikiforov V.S., Bondar S.S. Ickovich V.O. Changes in the content of components of IL/TOLL-signal pathway and NF-kB in mononuclear cells of whole blood under the influence of low-intensity electromagnetic radiation of 1 GHz. Geny i kletki. 2017; 12 (2): 90–6. doi: 10.23868/201707020 (in Russian).]
  21. Хадарцев А.А., Логаткина А.В., Терехов И.В., Бондарь С.С. Динамика проявлений метаболического синдрома у пациентов с артериальной гипертензией на фоне комплексного использования низкоинтенсивной микроволновой терапии. Артериальная гипертензия. 2018; 24 (2): 206–16. doi: 10.18705/1607-419X-2018-24-2-206-216 [Hadarcev A.A., Logatkina A.V., Terekhov I.V., Bondar S.S. Dynamics of manifestations of the metabolic syndrome in patients with arterial hypertension on the background of the complex use of low-intensity microwave therapy. Arterialnaya gipertenziya. 2018; 24 (2): 206–16. doi: 10.18705/1607-419X-2018-24-2-206-216 (in Russian).]

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