Pathogenic mechanisms of arterial hypertension in patients with chronic psychoemotional stress

The article is based on literature review and describes the implication of psycho-emotional factors in the development of arterial hypertension (HTN). HTN and its cardiovascular complications take a leading place among the causes of high mortality and disability in the adult population. High blood pressure (BP) is known to be a major modifiable risk factor for premature death, myocardial infarction, stroke and other cardiovascular diseases. The pathogenesis of HTN is complex and multifactorial with a significant variability of the involved mechanisms in individual patients. In this regard, the determination of specific pathogenic mechanisms underlying stable BP elevation would substantially individualize therapeutic approaches, and hence increase the effectiveness of treatment. The role of psycho-emotional stress has been recently reassessed and it is widely discussed as a factor contributing to the HTN formation. Global urbanization, sedentary lifestyle, daily work-related stress, lack of physical activity and social support lead to increased anxiety, uncertainty, and finally to chronic mental and emotional stress. This review analyzes the main physiological markers of chronic stress, neuroendocrine and immunological mechanisms underlying the development of HTN. The role of endothelial dysfunction as a binding link between chronic stress and high BP is also discussed.

1. World Health Organization (WHO). A Global Brief on Hypertension: Silent Killer, Global Public Health Crisis [Internet]. 2013. 40 p. [cited 2015 Dec 07]. Available from: http://apps.who.int/iris/bitstream/10665/79059/1/WHO_DCO_WHD_2013.2_eng.pdf

2. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M et al. Heart disease and stroke statistics-2015 update: a report from the american heart association [Internet]. Circulation. 2015;131(4):e29-e322. doi: 10.1161/CIR.0000000000000152 [cited 2015 Dec 07]. Available from: http://circ.ahajournals.org/content/131/4/e29.full.pdf+html

3. Chazova IE, Trubacheva IA, Zhernakova YuV, Oshchepkova EV, Serebriakova VN, Kaveshnikov VS. The prevalence of arterial hypertension as a risk factor of cardiovascular diseasesin one of the citiesin Siberian Federal District. Systemnye Gipertenzii = Systemic Hypertension. 2013;10(4):30–37.

4. Chazova IE. Hypertension: from A.L. Myasnikov to the present. Consilium medicum. 2014;16(12):5–9.

5. Nascimento BR, Brant LC, Moraes DN, Ribeiro AL. Global health and cardiovascular disease. Heart. 2014;100(22):1743–1749. doi:10.1136/heartjnl‑2014–306026.

6. Weber MA, Schiffrin EL, White WB, Mann S, Lindholm LH, Kenerson JG et al. Clinical practice guidelines for the management of hypertension in the community. J Clin Hypertens. 2014;16(1):14–26. doi: 10.1111/jch.12237.

7. Lutskiy IS, Zyablitsev SV, Lutskiy EI, Kishenya MS, Chernobrivtsev PA. Clinical and genetic aspects of arterial hypertension in condition of the chronic stress. Fundamentalnye Issledovaniya = Fundamental Research. 2014;10:1753–1758.

8. Osipova IV, Antropova ON, Golovina KG, Lobanova NA, Zaltsman AG, Kalinina IV. Masked hypertension in subjects with job-related stress. Arterialn’aya Gipertenziya = Arterial Hypertension. 2010;16(3):316–320.

9. Solodkov AP, Belyaeva LE, Lazuko SS. Stress and hypertension. Praktikyuchiy Likar. 2013;3:78–80.

10. Spruill TM. Chronic psychosocial stress andhypertension. Curr Hypertens Rep. 2010;12(1):10–16. doi: 10.1007/s11906–009–0084–8.

11. Backé E-M, Seidler A, Latza U, Rossnagel K, Schumann B. The role of psychosocial stress at work for the development of cardiovascular diseases: a systematic review. Intern Arch Occup Environ Health. 2012;85(1):67–79. doi:10.1007/s00420–011–0643–6.

12. Gafarova AV, Gafarov VV, Gromova EA, Gagulin IV. The effects of stress on risk of arterial hypertension in general male population of 25–64 years old: 14 years of follow up (epidemiological study on the basis of the WHO program «MONICA-PSYCHOSOCIAL»). Arterial’naya Gipertenziya = Arterial Hypertension. 2013;19(1):27–31.

13. Timio M. Blood pressure trend and psychosocial factors: the case of the nuns in a secluded order. Acta physiologica scandinavica. Supplementum. 1996;640:137–139.

14. Granado NS, Smith TC, Swanson GM, Harris RB, Shahar E, Smith B et al. Newly reported hypertension after military combat deployment in a large population-based study. Hypertension. 2009;54(5):966–973. doi: 10.1161/HYPERTENSIONAHA.109.132555.

15. Selye H. The essays of the adaptation syndrome. Moscow; 1960. 254 p.

16. Vodopianova NE. Psychodiagnostics of stress. SPb.: Piter; 2009. 336 p.

17. Cherkasova ES. Objective assessment chronic stress complicated by vegetative dysfunction in the officers of the Russian Investigative Committee. Psikhopedagogika v Pravookhranitelnykh Organakh = Psychopedagogicsin LawEnforcement Authorities. 2014;4(59):63–67.

18. Vetosheva VI, Volodina SO, Volodin VV. Ways of activation of protective mechanisms of a human organism at long acting stress. Izvestiya Komi Nauchnogog Zentra RAS = News of Komi Science Center. 2014;3(19):65–69.

19. Steptoe A, Kivimäki M. Stress and cardiovascular disease: an update on current knowledge. Ann Rev Public Health. 2013;34:337–354. doi: 10.1146/annurevpublhealth-031912–114452.

20. Krivolapchuk IA. Increasing the stress resistance in children by means of physical education. Physical culture, sport and tourism: scientific and methodological support. Materials of Russian scientific-practical conference with international participation. Perm. 2014:159–162.

21. Gerber M, Pühse U. Review article: do exercise and fitness protect against stress-induced health complaints? A review of the literature. Scandinavian J Public Health. 2009;37(8):801–19. doi: 10.1177/1403494809350522.

22. Holmes ME, Ekkekakis P, Eisenmann JC. The physical activity, stress and metabolic syndrome triangle: a guide to unfamiliar territory for the obesity researcher. Obes Rev. 2010;11(7):492–507. doi: 10.1111/j.1467–789X. 2009.00680.x.

23. Sothmann MS. The cross-stressor adaptation hypothesis and exercise training. Psychobiology of physical activity. Champaign, IL: Human Kinetics, 2006. 149–160 p.

24. Hamer M. Psychosocial stress and cardiovascular disease risk: the role of physical activity. Psychosom Med. 2012;74(9):896–903. doi: 10.1097/PSY.0b013e31827457f4.

25. Toker S, Biron M. Job burnout and depression: unraveling their temporal relationship and considering the role of physical activity. J Appl Psychol. 2012;97(3):699–710. doi: 10.1037/a0026914.

26. Forcier K, Stroud LR, Papandonatos GD, Hitsman B, Reiches M, Krishnamoorthy J. Links between physical fitness and cardiovascular reactivity and recovery to psychological stressors: A meta-analysis. Health Psychol. 2006;25(6):723–39.

27. Gasperin D, Netuveli G, Dias-da-Costa JS, PattussiMP. Effect of psychological stress on blood pressure increase: a meta-analysis of cohort studies. Cadernos de SaúdePública [Internet]. 2009;25(4):715–726. [cited 2015 Dec 08] Available from: http://www.scielosp.org/scielo.php?script=sci_arttext&pid=S0102–311X2009000400002&lng=en. http://dx.doi.org/10.1590/S0102–311X2009000400002

28. Huang C-J, Webb HE, Zourdos MC, Acevedo EO. Cardiovascular reactivity, stress, and physical activity. Front Physiol. 2013;4:314. doi: 10.3389/fphys.2013.00314.

29. Semyachkina-Glushkovskaya OV, Anishchenko TG, Berdnikova VA, Kuznetsova AS, Kuznetsova YaV et al. Cardiovascular stress-reactivity as the indicator of hypertension development. Proceedings of the Samara Scientific Center of the Russian Academy of Sciences. 2009;11:1027–1030.

30. Lang GF. Hypertension. Leningrad: Medgiz, 1950. p. 496.

31. Miasnikov AL. Hypertension. Moscow: Medgiz, 1952. p. 392.

32. Folkow B. Physiological aspects of primary hypertension. Physiol Rev. 1982;62(2):347–504.

33. Henry JP, Liu YY, Nadra WE, Qian CG, Mormede P, Lemaire V et al. Psychosocial stress can induce chronic hypertension in normotensive strains of rats. Hypertension. 1993;21(5):714–723. doi: 10.1161/01.HYP.21.5.714.

34. Grassi G, Seravalle G, Quarti-Trevano F. The ‘neuroadrenergic hypothesis’ in hypertension: current evidence. Experim Physiol. 2010;95(5):581–586. doi:10.1113/expphysiol.2009.047381.

35. Esler M, Eikelis N, Schlaich M, Lambert G, Alvarenga M, Dawood T et al. Chronic mental stress is a cause of essential hypertension: presence of biological markers of stress. Clin Experim Pharmacol Physiol. 2008;35 (4):498–502. doi: 10.1111/j.1440–1681.2008.04904.x.

36. Kozlova MA, Kozlov AI. Cortisol as a marker of stress. Hum Physiol. 2014;40(2):123–136.

37. Guilliams TG, Edwards L. Chronic stress and the HPA axis. The Standard. 2010;9(2):1–12.

38. Gadinger MC, Loerbroks A, Schneider S, Thayer JF, Fischer JE. Associations between job strain and the cortisol/DHEA-S ratio among management and nonmanagement personnel. Psychosom Med. 2011;73 (1):44–52. doi: 10.1097/PSY.0b013e3181fc6fe8.

39. Davidovich IM, Afonaskov OV. Arterial hypertension in young officers of land forces: psychophysiological peculiarities. Vestnik Roszdravnadzora. 2012;5:51–55.

40. Thayer JF, Ahs F, Fredrikson M, Sollers JJ, Wager TD. A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health. Neurosci Biobehav Rev. 2012;36(2):747–756. doi: 10.1016/j.neubiorev.2011.11.009.

41. Landsbergis PA, Dobson M, Koutsouras G, Schnall P. Job strain and ambulatory blood pressure: a metaanalysis and systematic review. Am J Public Health. 2013;103 (3): e61-e71. doi: 10.2105/AJPH.2012.301153.

42. Fan L, Blumenthal JA, Hinderliter AL, Sherwood A. The effect of job strain on nighttime blood pressure dipping among men and women with high blood pressure. Scand J Work Environ Health. 2013;39(1):112–119. doi: 10.5271/sjweh.3294.

43. Mancia G, Grassi G. The autonomic nervous system and hypertension. Circul Res. 2014;114(11):1804–1814. doi: 10.1161/CIRCRESAHA.114.302524.

44. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983;24 (4):385–396.

45. Karasek R, Brisson C, Kawakami N, Houtman I, Bongers P, Amick B. The Job Content Questionnaire (JCQ): an instrument for internationally comparative assessments of psychosocial job characteristics. J Occup Health Psychol. 1998;3(4):322–355. doi: 10.1037/1076–8998.3.4.322.

46. Siegrist J, Starke D, Chandola T, Godin I, Marmot M, Niedhammer I et al. The measurement of effortreward imbalance at work: European comparisons. Soc Sci Med. 2004;58(8):1483–1499. doi: 10.1016/S0277–9536 (03)00351–4.

47. Gilbert-Ouimet M, Trudel X, Brisson C, Milot A, Vézina M. Adverse effects of psychosocial work factors on blood pressure: systematic review of studies on demandcontrol-support and effort–reward imbalance models. Scand J Work Environ Health. 2014;40(2):109–132. doi:10.5271/sjweh.3390.

48. Sobchik LN. A standardized method of multivariate study of personality SMSP. St Petersburg: Rech, 2000. P. 219.

49. Hamilton M. The Hamilton rating scale for depression. In: Ban TA, Sartorius N, editors. Assessment of depression. Springer Berlin Heidelberg, 1986. P. 143–152.

50. Khanin YuL. Manual for the State-Trait Anxiety Inventory by Spielberger CD. Leningrad: LNIIFK, 1976. 18 p.

51. Gafarov VV, Panov DO, Gromova EA, Gagulin IV, Gafarova AV. Risk of arterial hypertension and personal anxiety in 25–64 years old female population: a 16 year old epidemiological study based on the WHO program “MONICA PSYCHOSOCIAL”. Arterial’naya Gipertenziya = Arterial Hypertension. 2012;4(18):298–302.

52. Podolsky AV, Steblyuk VV. Level of stressor tension and evaluation of quality of life in patients with hypertension. Mir Mediciny i Biologii = The World of Medicine and Biology. 2014;3(45):90–93.

53. Antonysheva OV. Adverse events in patients with hypertension II degree with different levels of anxiety, depression and cognitive impairment. Vestnik VSMU = Bulletin of VSMU. 2103;12(4):92–99.

54. Cohen S, Janicki-Deverts D, Doyle WJ, Miller GE, Frank E, Rabin BS et al. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proceed Nation Acad Sci. 2012;109(16):5995–5999. doi: 10.1073/pnas.1118355109.

55. Gouin JP, Glaser R, Malarkey WB, Beversdorf D, Kiecolt-Glaser J. Chronic stress, daily stressors, and circulating inflammatory markers. Health Psychol. 2012;31 (2):264–268. doi: 10.1037/a0025536.

56. Nakata A. Psychosocial job stress and immunity: a systematic review. Psychoneuroimmunology. Human Press. 2012;934:39–75. doi: 10.1007/978–1-62703–071–7_3.

57. Rohleder N. Stimulation of systemic low-grade inflammation by psychosocial stress. Psychosom Med. 2014;76(3):181–189. doi: 10.1097/PSY.0000000000000049.

58. Harrison DG, Guzik TG, Lob H, Madhur M, MarvarPJ, Thabet S et al. Inflammation, immunity, and hypertension. Hypertension. 2011;57(2):132–140. doi: 10.1161/HYPERTENSIONAHA.110.163576.

59. Wenzel U, Turner JE, Krebs C, Kurts C, Harrison DG, Ehmke H. Immune mechanisms in arterial hypertension [Internet]. J Am Soc Nephrol. 2015. doi: 10.1681/ASN.2015050562 [cited 2015 Dec 08]. Available from: http://jasn.asnjournals.org/content/early/2015/08/28/ASN.2015050562.full.pdf+html

60. Non AL, Rimm EB, Kawachi I, Rewak MA, Kubzansky LD. The effects of stress at work and at home on inflammation and endothelial dysfunction [Internet]. PloS one. 2014;9(4): e94474. doi: 10.1371/journal.pone.0094474 [cited 2015 Dec 08]. Available from: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0094474

61. Kim YW, West XZ, Byzova TV. Inflammation and oxidative stress in angiogenesis and vascular disease. J Mol Med. 2013;91(3):323–328. doi: 10.1007/s00109–013–1007–3.

62. Dinh QN, Drummond GR, Sobey CG, Chrissobolis S. Roles of inflammation, oxidative stress, and vascular dysfunction in hypertension [Internet]. BioMed Res Intern. 2014; Article ID 406960. doi: 10.1155/2014/406960 [cited 2015 Dec 08]. Available from: http://www.hindawi.com/journals/bmri/2014/406960/

63. Amati M, Tomasetti M, Ciuccarelli M, Mariotti L, Tarquini LM, Bracci M et al. Relationship of job satisfaction, psychological distress and stress-related biological parameters among healthy nurses: a longitudinal study. J Occup Health. 2010;52(1):31–38. doi: org/10.1539/joh.L9042.

64. Yoon HS, Lee KM, Kang D. Intercorrelation between immunological biomarkers and job stressindicators among female nurses: a 9-month longitudinal study [Internet]. Frontiers in public health. 2014;2:157. doi: 10.3389/fpubh.2014.00157 [cited 2015 Dec 08]. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195281/

65. Marvar PJ, Vinh A, Thabet S, Lob HE, Geem D, Ressler KJ et al. T lymphocytes and vascular inflammation contribute to stress-dependent hypertension. Biol Psychiatry. 2012;71(9):774–782. doi: 10.1016/j.biopsych.2012.01.017.

66. Nakata A, Takahashi M, Irie M. Effortreward imbalance, overcommitment, and cellular immune measures among white-collar employees. Biol Psychol. 2011;88 (2):270–279. doi: 10.1016/j.biopsycho.2011.08.012.

67. Copertaro A, Bracci M, Gesuita R, Carle F, Amati M, Baldassari M et al. Influence of shift-work on selected immune variables in nurses. Industrial Health. 2011;49(5):597–604. doi.org/10.2486/indhealth.MS1210.

68. Crowley SD. The cooperative roles of inflammation and oxidative stress in the pathogenesis of hypertension. Antioxidants Redox Signaling. 2014;20(1):102–120.

69. doi:10.1089/ars.2013.5258.

70. Schiffrin EL. The immune system: role in hypertension. Can J Cardiol. 2013;29(5):543–548. doi: 10.1016/j.cjca.2012.06.009.

71. Coffman TM. Under pressure: the search for the essential mechanisms of hypertension. Nature Med. 2011;17 (11):1402–1409. doi:10.1038/nm.2541.

72. Adamenko GP, Golovko ES, Skreblo EI, Tihon TV. Markers of intravascular inflammation and cytokine profile in arterial hypertension. Probl Health Ecol. 2014;2:40–44.

73. Newton K, Dixit VM. Signaling in innate immunity andinflammation [Internet]. Cold Spring Harbor perspectivesin biology. 2012;4(3). doi: 10.1101/cshperspect.a006049 [cited 2015 Dec 09]. Available from: http://cshperspectives.cshlp. org/content/4/3/a006049.short

74. Jiménez MC, Rexrode KM, Glynn RJ, Ridker PM, Gaziano JM, Sesso HD. Association between high-sensitivity c-reactive protein and total stroke by hypertensive status among men [Internet]. J Am Heart Assoc. 2015;4 (9): e002073. doi: 10.1161/JAHA.115.002073 [cited 2015 Dec 09]. Available from: http://jaha.ahajournals.org/content/4/9/e002073.full.pdf+html

75. The Emerging Risk Factors Collaboration. C-reactive protein, fibrinogen, and cardiovascular disease prediction. N Engl J Med. 2012;367(14):1310–1320. doi: 10.1056/NEJMoa1107477.

76. Hage FG. C-reactive protein and hypertension. J Hum Hypertens. 2014;28(7):410–415. doi:10.1038/jhh.2013.111.

77. Kong H, Qian YS, Tang XF, Zhang J, Gao PJ, ZhangY et al. C-reactive protein (CRP) gene polymorphisms, CRP levels and risk of incident essential hypertension: findings from an observational cohort of Han Chinese. Hypertens Res. 2012;35(10):1019–1023. doi: 10.1038/hr.2012.89.

78. Vasilez LM, Grigoriadi NE, Gordiichuk RN, Karpunina NS, Krivaya AA, Scherbenev VM. The features of the inflammation indicators in the group of the patients with the arterial hypertension. Sovremennye Problemy Nauki i Obrazovaniya = Modern Problems of Science and Education. 2012;6:211–216.

79. Khanmurzayeva NB, Mammaev SN. Relationship of cytokines with the degree of increase in blood pressure in patients with essential hypertension. Meditsina i Obrazovaniye v Sibiri = Medicine and Education in Siberia. 2013;6.

80. Sabanayagam C, Shankar A, Lee J, Wong TY, Tai ES. Serum C-reactive protein level and prehypertension in two Asian populations. J Hum Hypertens. 2013;27(4):231–236. doi: 10.1038/jhh.2011.117.

81. King DE, Egan BM, Mainous AG, Geesey ME. Elevation of C-reactive protein in people with prehypertension. J Clin Hypertens. 2004;6(10):562–568.

82. Cheung BM, Ong KL, Tso AW, Leung RY, Xu A, Cherny SS et al. C-reactive protein as a predictor of hypertension in the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) cohort. J Hum Hypertens. 2012;26(2):108–116. doi: 10.1038/jhh.2010.125.

83. Shivpuri S, Gallo LC, Crouse JR, Allison MA. The association between chronic stress type and C-reactive protein in the multi-ethnic study of atherosclerosis: does gender make a difference? J Behav Med. 2012;35(1):74–85. doi: 10.1007/s10865–011–9345–5.

84. Copeland WE, Shanahan L, Worthman C, AngoldA, Costello EJ. Cumulative depression episodes predicts later C-reactive protein levels: a prospective analysis. Biol Psychiatry. 2012;71(1):15–21. doi: 10.1016/j.biopsych.2011. 09.023.

85. Carpenter LL, Gawuga CE, Tyrka AR, Price LH. C-reactive protein, early life stress, and wellbeing in healthy adults. Acta Psychiatrica Scandinavica. 2012;126(6):402–410. doi: 10.1111/j.1600–0447.2012.01892.x.

86. Wium-Andersen M, Orsted D, Nielsen S, Nordestgaard B. Elevated C-reactive protein levels, psychological distress, and depression in 73 131 individuals. J Am Med Assoc Psychiatry. 2013;70(2):176–184. doi:10.1001/2013.jamapsychiatry.102.

87. Copeland WE, Shanahan L, Worthman C, Angold A, Costello EJ. Generalized anxiety and C-reactive protein levels: a prospective, longitudinal analysis. Psychol Med. 2012;42 (12):2641–2650. doi: 10.1017/S0033291712000554.

88. Vostrokova NV, Fyodorov DV, Mamayev AN, KlimovaYeYe, Bishevski KM, BelykhVI. Markers ofinflammatory reaction (C-reactive protein and interleukin-6) in arterial hypertension. Sibirskij Meditsinskij Zhurnal = Siberian Medical Journal. 2009;4(1):33–35.

89. Chamarthi B, Williams GH, Ricchiuti V, Srikumar N, Hopkins PN, Luther JM et al. Inflammation and hypertension: the interplay of interleukin-6, dietary sodium, and the renin–angiotensin system in humans. Am J Hypertens. 2011;24 (10):1143–1148. doi: 10.1038/ajh.2011.113.

90. Radaeva OA, Novikova LV. The system of IL-6 as a risk factor of urgent critical condition development in patients with essential hypertension. Fundamentalnye Issledovaniya = Fundamental Research. 2012;10:103–107.

91. Lukic L, Lalic NM, Rajkovic N, Jotic A, Lalic K, Milicic T et al. Hypertension in obese type 2 diabetes patients is associated with increases in insulin resistance and IL‑6 cytokine levels: potential targets for an efficient preventive intervention. Intern J Environ Res Public Health. 2014;11(4):3586–3598. doi: 10.3390/ijerph110403586.

92. Hamer M, Steptoe A. Association between physical fitness, parasympathetic control, and proinflammatory responses to mental stress. Psychosom Med. 2007;69 (7):660–6. doi: 10.1097/PSY.0b013e318148c4c0.

93. Tsioufis C, Kordalis A, Flessas D, AnastasopoulosI, Tsiachris D, Papademetriou V et al. Pathophysiology of resistant hypertension: the role of sympathetic nervous system [Internet]. Intern J Hypertens. 2011;2011:642416. doi: 10.4061/2011/642416 [cited 2015 Dec 09]. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034926/

94. Bolívar JJ. Essential hypertension: an approach to its etiology and neurogenic pathophysiology [Internet]. Intern J Hypertens. 2013;2013:547809. doi:10.1155/2013/547809 [cited 2015 Dec 09]. Available from: http://www.hindawi.com/journals/ijhy/2013/547809/cta/

95. Parati G, Esler M. The human sympathetic nervous system: its relevance in hypertension and heart failure. Eur Heart J. 2012;33(9):1058–1066. doi: org/10.1093/eurheartj/ehs041.

96. Bergmann N, Gyntelberg F, Faber J. The appraisal of chronic stress and the development of the metabolic syndrome: a systematic review of prospective cohort studies. Endocrine Connections. 2014;3(2): R55-R80. doi: 10.1530/EC-14–0031.

97. Chopra S, Baby C, Jacob JJ. Neuro-endocrine regulation of blood pressure. Ind J Endocrinol Metab. 2011;15 (Suppl4): S281-S288. doi: 10.4103/2230–8210.86860.

98. Hasnulin VI, Hasnulina AV, Chechetkina II. The northern stress, arterial hypertension in the north, approach to prophylaxis and treatment. Ekologiya Cheloveka = Human ecology. 2009;6:26–30.

99. Ermakova MA, Aftanas LI, Shpagina LA. Characteristics of psychophysiological stress markers in patients with arterial hypertension depending on the level of occupational risk. Bulletin SO RAMN. 2014;34(4):36–41.

100. González-Cabrera J, Fernández-Prada M, IribarIbabe C, Peinado JM. Acute and chronic stress increase salivary cortisol: a study in the real-life setting of a national examination undertaken by medical graduates. Stress. 2014;17 (2):149–156. doi: 10.3109/10253890.2013.876405.

101. Izawa S, Saito K, Shirotsuki K, Sugaya N, Nomura S. Effects of prolonged stress on salivary cortisol and dehydroepiandrosterone: A study of a two-week teaching practice. Psychoneuroendocrinology. 2012;37(6):852–858. doi: 10.1016/j.psyneuen.2011.10.001.

102. Alleva E, Petruzzi S, Cirulli F, Aloe L. NGF regulatory role in stress and coping of rodents and humans. Pharmacol Biochem Behav. 1996;54(1):65–72.

103. Aloe L, Alleva E, Fiore M. Stress and nerve growth factor: findings in animal models and humans. Pharmacol Biochem Behav. 2002;73(1):159–166.

104. Aloe L, Rocco ML, Bianchi P, Manni L. Nerve growth factor: from the early discoveries to the potential clinical use. J Transl Med. 2012;10:239. doi: 10.1186/1479–5876–10–239.

105. Yanev S, Aloe L, Fiore M, Chaldakov GN. Neurotrophic and metabotrophic potential of nerve growth factor and brain-derived neurotrophic factor: linking cardiometabolic and neuropsychiatric diseases. World J Pharmacol. 2013;2:92–99. doi: 10.5497/wjp.v2.i4.92.

106. Bunting S, Gryglewski R, Moncada S, Vane JR. Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which relaxes strips of mesenteric and coeliac arteries and inhibits platelet aggregation. Prostaglandins. 1976;12(60):897–913.

107. Weksler BB, Marcus AJ, Jaffe EA. Synthesis of prostaglandin I2 (prostacyclin) by cultured human and bovine endothelial cells. Proceed Nation Acad Sci. 1977;74 (9):3922–3926.

108. Bernatova I. Endothelial dysfunction in experimental models of arterial hypertension: cause or consequence? [Internet] BioMed ResIntern. 2014;2014:598271. doi: 10.1155/2014/598271 [cited 2015Dec 09]. Available from: http://www.hindawi.com/journals/bmri/2014/598271/

109. Rafikov R, Fonseca FV, Kumar S, Pardo D, Darragh C, Elms S et al. eNOS activation and NO function: structural motifs responsible for the posttranslational control of endothelial nitric oxide synthase activity. J Endocrinol. 2011;210(3):271–284. doi: 10.1530/JOE-11–0083.

110. Bird IM. Endothelial nitric oxide synthase activation and nitric oxide function: new light through old windows. J Endocrinol. 2011;210(3):239–241. doi: 10.1530/JOE-11–0216.

111. Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33(7):829–837. doi: 10.1093/eurheartj/ehr304.

112. Shi Y, Vanhoutte PM. Reactive oxygen species and endothelium-derived contracting factor (EDCF) partners in endothelial dysfunction. Systems Biology of Free Radicals and Antioxidants. Springer Berlin Heidelberg. 2014;1325–1342. doi: 10.1007/978–3-642–30018–9_74.

113. Bruno RM, Ghiadoni L, Seravalle G, Dell’Oro R, Taddei S, Grassi G. Sympathetic regulation of vascular function in health and disease. Front Physiol. 2012;3:284. doi: 10.3389/fphys.2012.00284.

114. Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S. Endothelium-dependent contractions and endothelial dysfunction in human hypertension. Br J Pharmacol. 2009;157(4):527–536. doi: 10.1111/j.1476–5381.2009.00240.x.

115. Popova AA, Berezikova EN, Mayanskaya SD. Mechanism of endothelial dysfunction development. Sibirskoye Meditsinskoye Obozreniye = Siberian Medical Review. 2010;64(4).

116. Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S. Endothelial dysfunction as a target for prevention of cardiovascular disease. Diabetes Care. 2009;32 (Suppl 2): S314-S321. doi: 10.2337/dc09-S330.

117. Popova AA, Mayanskaya SD, Mayanskaya NN, Berezikova EI, Khidirova LD. Arterial hypertension and endolelium dysfunction (part 1). Journal of Modern Clinical Medicine. 2009;2(2):42–46.

118. Lekakis J, Abraham P, Balbarini A, Blann A, Boulanger CM, Cockcroft J et al. Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation. Eur J Cardiovasc Prevent Rehabil. 2011;18 (6):775–789. doi: 10.1177/1741826711398179.

119. Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P et al. The assessment of endothelial function from research into clinical practice. Circulation. 2012;126(6):753–767. doi: 10.1161/CIRCULATIONAHA.112.093245

120. Toda N, Nakanishi-Toda M. How mental stress affects endothelial function. Pflügers Archive. 2011;462 (6):779–794. doi: 10.1007/s00424–011–1022–6.

121. vonKänel R. Psychosocial stress and cardiovascular risk: current opinion [Internet]. Swiss Med Wkly. 2012;142: w13502 [cited 2015 Dec 09]. doi: 10.4414/smw.2012.13502. Available from: http://www.smw.ch/content/smw-2012–13502/

122. Chung IM, Kim HY, Lee YJ. Psychological stress impairs both endothelial function and insulin sensitivity via activation of inflammation and ER stress pathways mediated by corticotropin-releasing hormone [Internet]. Arterioscl Thromb Vasc Biol. 2014;34 (Suppl 1): A340 [cited 2015 Dec 09]. Available from: http://atvb.ahajournals.org/content/34/Suppl_1/A340.short

123. Spieker LE, Hürlimann D, Ruschitzka F, Corti R, Enseleit F, Shaw S et al. Mental stress induces prolonged endothelial dysfunction via endothelin-A receptors. Circulation. 2002;105(24):2817–2820.

124. Gu H, Tang C, Yang Y. Psychological stress, immune response, and atherosclerosis. Atherosclerosis. 2012;223 (1):69–77. doi: 10.1016/j.atherosclerosis.2012.01.021.

125. Golbidi S, Frisbee JC, LaherI. Chronic stressimpacts the cardiovascular system: animal models and clinical outcomes. Am J Physiol. Heart Circul Physiol. 2015;308 (12):1476–1498. doi: 10.1152/ajpheart.00859.2014.

126. Omelyanenko MG, Shumakova VA, Suhovey NA, Schapova NN. Psychoemotional disorders and endothelial disfunction in cardiovascular diseases associated with atherosclerosis. Sibirskij Meditsinskij Zhurnal = Siberian Medical Journal. 2014;29(3):18–24.

127. Mausbach BT, Roepke SK, Ziegler MG, Milic M, Känel R, Dimsdale JE et al. Association between chronic caregiving stress and impaired endothelial function in the elderly. J Am Coll Cardiol. 2010;55(23):2599–2606. doi: 10.1016/j.jacc.2009.11.093

128. Lutskiy IS, Zyablitsev SV, Lutskiy EI, Kishenya MS, Chernobrivtsev PA. Clinical and genetic aspects of the arterial hypertension in condition of the chronic stress. Fundamentalnye Issledovaniya = Fundamental research. 2014;10:1753–1758.

129. Kim HS, Cho KI. Impact of chronic emotional stress on myocardial function in postmenopausal women and its relationship with endothelial dysfunction. Korean Circul J. 2013;43 (5):295–302. doi: 10.4070/kcj.2013.43.5.295.

130. Ghiadoni L, Taddei S, Virdis A. Hypertension and endothelial dysfunction: therapeutic approach. Curr Vasc Pharmacol. 2012;10(1):42–60.

131. Puddu P, Puddu GM, Cravero E, Vizioli L, Muscari A. The relationships among hyperuricemia, endothelial dysfunction, and cardiovascular diseases: molecular mechanisms and clinical implications. J Cardiol. 2012;59(3):235–242. doi: 10.1016/j.jjcc.2012.01.013.

132. Vizir VA, Berezin AE. The role of endothelial dysfunction in formation and progression of arterial hypertension. Prognostic value and treatment prospects. Ukrainian Medical Journal. 2000;4:23–33.

133. Grebenkina IA, Mayanskaya SD, Popova AA, Luksha EB. State vasomotor function of endothelia in young persons with weighed down by history of arterial hypertension. Practice Medicine. 2011;4(52):37–41.

134. Kietadisorn R, Juni RP, Moens AL. Tackling endothelial dysfunction by modulating NOS uncoupling: new insightsinto its pathogenesis and therapeutic possibilities. Am J Physiol Endocrin Metab. 2012;302(5):481–495. doi: 10.1152/ajpendo.00540.2011.

135. Stewart DJ. Clinical relevance of endothelial dysfunction in cardiovascular disorders. Agents and Actions. Supplements. 1995;45:227–235.

136. Popova AA, Mayanskaya SD, Mayanskaya NN, Berezikova EI, Khidirova LD. Arterial hypertension and endolelium dysfunction (part 2). Journal of Modern Clinical Medicine. 2009;2(3):43–48.

137. Schulz E, Gori T, Münzel T. Oxidative stress and endothelial dysfunction in hypertension. Hypertens Res. 2011;34(6):665–673. doi: 10.1038/hr.2011.39.