Arterial hypertension: possible pathogenetic mechanisms for the development of chronic brain ischemia

DOI: https://doi.org/10.29296/25877305-2020-09-01
Download full text PDF
Issue: 
9
Year: 
2020

Professor E. Barinov, MD; T. Faber; V. Sokhina M. Gorky Donetsk National Medical University,
Ukraine

Arterial hypertension is considered as a risk factor for the development of chronic cerebral ischemia (CСI) but the causes of this phenomenon remain poorly understood. Due to the role and interaction of the sympathoadrenal and renin-angiotensin systems of the body in impaired function of the «vessel-glia-neuron» system is discussed. The review presents facts regarding the features of adrenergic regulation of cerebral circulation, the possible participation of adrenoreceptors in cognitive impairment and the development of neuroinflammation. The relationship of angiotensin-2 with remodeling of the vascular wall and the permeability of the blood-brain barrier, activation of glial cells is considered. These data substantiate the need to study selective agonists of α-, β-adrenergic receptors and blockers of AT1 receptors for the treatment of patients with cerebrovascular disorders.
Keywords: 
neurology
hematology
cardiology
arterial hypertension
chronic brain ischemia
adrenergic receptors
renin-angiotensin system

It appears your Web browser is not configured to display PDF files. Download adobe Acrobat или click here to download the PDF file.

References: 
  1. Von Känel R., Dimsdale J. Effects of sympathetic activation by adrenergic infusions on hemostasis in vivo. Eur J Haematol. 2000 ;65 (6): 357–69. DOI: 10.1034/j.1600-0609.2000.065006357.x
  2. Jordan J. Device-Based Approaches for the Treatment of Arterial Hypertension. Curr Hypertens Rep. 2017; 19 (7): 59. DOI: 10.1007/s11906-017-0755-9
  3. Diaz-Cabiale Z., Parrado C., Fuxe K. et al. Receptor-receptor interactions in central cardiovascular regulation. Focus on neuropeptide/alpha(2)-adrenoreceptor interactions in the nucleus tractus solitaries. J Neural Transm (Vienna). 2007; 114 (1): 115–25. DOI: 10.1007/s00702-006-0559-6
  4. McGrath J. Localization of α-adrenoceptors: JR Vane Medal Lecture. Br J Pharmacol. 2015; 172 (5): 1179–94. DOI: 10.1111/bph.13008
  5. Conti V., Russomanno G., Corbi G. et al. Adrenoreceptors and nitric oxide in the cardiovascular system. Front Physiol. 2013; 4: 321. DOI: 10.3389/fphys.2013.00321
  6. Purkayastha S., Saxena A., Eubank W. et al. α1-Adrenergic receptor control of the cerebral vasculature in humans at rest and during exercise. Exp Physiol. 2013; 98 (2): 451–61. DOI: 10.1113/expphysiol.2012.066118
  7. Kaya S., Kolodjaschna J., Berisha F. et al. Effect of the α(2)-adrenoceptor antagonist yohimbine on vascular regulation of the middle cerebral artery and the ophthalmic artery in healthy subjects. Microvasc Res. 2011; 81 (1): 117–22. DOI: 10.1016/j.mvr.2010.10.001
  8. Diaz H., Toledo C., Andrade D. et al. Neuroinflammation in heart failure: NEW insights for an old disease. J Physiol. 2020; 598 (1): 33–59. DOI: 10.1113/JP278864
  9. Harris N., Isaac A., Günther A. et al. Dorsal BNST α2A-Adrenergic Receptors Produce HCN-Dependent Excitatory Actions That Initiate Anxiogenic Behaviors. J Neurosci. 2018; 38 (42): 8922–42. DOI: 10.1523/JNEUROSCI.0963-18.2018
  10. Vucicevic J., Nikolic K., Dobričić V. et al. Prediction of blood-brain barrier permeation of α-adrenergic and imidazoline receptor ligands using PAMPA technique and quantitative-structure permeability relationship analysis. Eur J Pharm Sci. 2015; 68: 94–105. DOI: 10.1016/j.ejps.2014.12.014
  11. Nguyen V., Tiemann D., Park E. et al. Alpha-2 Agonists. Anesthesiol Clin. 2017; 35 (2): 233–45. DOI: 10.1016/j.anclin.2017.01.009
  12. Andrews G., Lavin A. Methylphenidate increases cortical excitability via activation of alpha-2 noradrenergic receptors. Neuropsychopharmacology. 2006; 31 (3): 594–601. DOI: 10.1038/sj.npp.1300818
  13. Nguyen P., Connor S. Noradrenergic Regulation of Hippocampus-Dependent Memory. Cent Nerv Syst Agents Med Chem. 2019; 19 (3): 187–96. DOI: 10.2174/1871524919666190719163632
  14. Gao V., Suzuki A., Magistretti P. et al. Astrocytic β2-adrenergic receptors mediate hippocampal long-term memory consolidation. Proc Natl Acad Sci USA. 2016; 113 (30): 8526–31. DOI: 10.1073/pnas.1605063113
  15. Zhang W., Carreño F., Cunningham J. et al. Chronic sustained hypoxia enhances both evoked EPSCs and norepinephrine inhibition of glutamatergic afferent inputs in the nucleus of the solitary tract. J Neurosci. 2009; 29 (10): 3093–102. DOI: 10.1523/JNEUROSCI.2648-08
  16. Mather M., Clewett D., Sakaki M. et al. Norepinephrine ignites local hotspots of neuronal excitation: How arousal amplifies selectivity in perception and memory. Behav Brain Sci. 2016; 39: e200. DOI: 10.1017/S0140525X15000667
  17. Elenkov I., Wilder R., Chrousos G. et al. The sympathetic nerve – an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. 2000; 52 (4): 595–638.
  18. Roth S., Singh V., Tiedt S. et al. Brain-released alarmins and stress response synergize in accelerating atherosclerosis progression after stroke. Sci Transl Med. 2018; 10 (432): eaao1313. DOI: 10.1126/scitranslmed.aao1313
  19. Schlachetzki J., Fiebich B., Haake E. et al. Norepinephrine enhances the LPS-induced expression of COX-2 and secretion of PGE2 in primary rat microglia. J Neuroinflammation. 2010; 7: 2. DOI: 10.1186/1742-2094-7-2
  20. Cui C., Xu P., Li G. et al. Vitamin D receptor activation regulates microglia polarization and oxidative stress in spontaneously hypertensive rats and angiotensin II-exposed microglial cells: Role of renin-angiotensin system. Redox Biol. 2019; 26: 101295. DOI: 10.1016/j.redox.2019.101295
  21. Ren L., Lu X., Danser A. Revisiting the Brain Renin-Angiotensin System-Focus on Novel Therapies. Curr Hypertens Rep. 2019; 21 (4): 28. DOI: 10.1007/s11906-019-0937-8
  22. Haspula D., Clark M. Neuroinflammation and sympathetic over activity: Mechanisms and implications in hypertension. Auton Neurosci. 2018; 210: 10–7. DOI: 10.1016/j.autneu.2018.01.002
  23. Don-Doncow N., Vanherle L., Zhang Y. et al. T-Cell Accumulation in the Hypertensive Brain: A Role for Sphingosine-1-Phosphate-Mediated Chemotaxis. Int J Mol Sci. 2019; 20 (3): E537. DOI: 10.3390/ijms20030537
  24. Yu Y., Cao Y., Bell B. et al. Brain TACE (Tumor Necrosis Factor-α-Converting Enzyme) Contributes to Sympathetic Excitation in Heart Failure Rats. Hypertension. 2019; 74 (1): 63–72. DOI: 10.1161/HYPERTENSIONAHA.119.12651
  25. Singh R., Hristova K., Fedacko J. et al. Chronic heart failure: a disease of the brain. Heart Fail Rev. 2019; 24 (2): 301–7. DOI: 10.1007/s10741-018-9747-3
  26. Wright J., Harding J. Contributions by the Brain Renin-Angiotensin System to Memory, Cognition, and Alzheimer’s Disease. J Alzheimers Dis. 2019; 67 (2): 469–80. DOI: 10.3233/JAD-181035
  27. Sunami E., Nomura K., Nishiyama Y. et al. Effects of Candesartan Cilexetil Compared with Amlodipine on Serum Asymmetric Dimethylarginine Levels in the Chronic Stage of Cerebral Infarction: A Preliminary Study. J Nippon Med Sch. 2016; 83 (6): 272–6. DOI: 10.1272/jnms.83.272
  28. Lu J., Xu F., Zhang J. Inhibition of angiotensin II-induced cerebrovascular smooth muscle cell proliferation by LRRC8A downregulation through suppressing PI3K/AKT activation. Hum Cell. 2019; 32 (3): 316–25. DOI: 10.1007/s13577-019-00260-6
  29. Masi S., Uliana M., Virdis A. Angiotensin II and vascular damage in hypertension: Role of oxidative stress and sympathetic activation. Vascul Pharmacol. 2019; 115: 13–7. DOI: 10.1016/j.vph.2019.01.004
  30. Gurnik S., Devraj K., Macas J. et al. Angiopoietin-2-induced blood-brain barrier compromise and increased stroke size are rescued by VE-PTP-dependent restoration of Tie2 signaling. Acta Neuropathol. 2016; 131 (5): 753–73. DOI: 10.1007/s00401-016-1551-3
  31. Mukerjee S., Gao H., Xu J. et al. ACE2 and ADAM17 Interaction Regulates the Activity of Presympathetic Neurons. Hypertension. 2019; 74 (5): 1181–91. DOI: 10.1161/HYPERTENSIONAHA.119.13133
  32. Higaki A., Mogi M., Iwanami J. et al. Beneficial Effect of Mas Receptor Deficiency on Vascular Cognitive Impairment in the Presence of Angiotensin II Type 2 Receptor. J Am Heart Assoc. 2018; 7 (3): e008121. DOI: 10.1161/JAHA.117.008121
  33. Toledo C., Andrade D., Diaz H. et al. Neurocognitive Disorders in Heart Failure: Novel Pathophysiological Mechanisms Underpinning Memory Loss and Learning Impairment. Mol Neurobiol. 2019; 56 (12): 8035–51. DOI: 10.1007/s12035-019-01655-0
  34. Gupta V., Dhull D., Joshi J. et al. Neuroprotective potential of azilsartan against cerebral ischemic injury: Possible involvement of mitochondrial mechanisms. Neurochem Int. 2019; 132: 104604. DOI: 10.1016/j.neuint.2019.104604
  35. Fan L., Geng L., Cahill-Smith S. Nox2 contributes to age-related oxidative damage to neurons and the cerebral vasculature. J Clin Invest. 2019; 129 (8): 3374–86. DOI: 10.1172/JCI125173
  36. Huang X., Lu G., Li G.. et al. Dynamic Changes in the Renin-Angiotensin-Aldosterone System and the Beneficial Effects of Renin-Angiotensin-Aldosterone Inhibitors on Spatial Learning and Memory in a Rat Model of Chronic Cerebral Ischemia. Front Neurosci. 2017; 11: 359. DOI: 10.3389/fnins.2017.00359
  37. Salmani H., Hosseini M., Baghcheghi Y. et al. Losartan modulates brain inflammation and improves mood disorders and memory impairment induced by innate immune activation: The role of PPAR-γ activation. Cytokine. 2020; 125: 154860. DOI: 10.1016/j.cyto.2019.154860
  38. Saavedra J. Evidence to Consider Angiotensin II Receptor Blockers for the Treatment of Early Alzheimer’s Disease. Cell Mol Neurobiol. 2016; 36 (2): 259–79. DOI: 10.1007/s10571-015-0327-y
  39. Panahpour H., Nekooeian A., Dehghani G. Blockade of Central Angiotensin II AT1 Receptor Protects the Brain from Ischemia / Reperfusion Injury in Normotensive Rats. Iran J Med Sci. 2014; 39 (6): 536–42.
  40. Timaru-Kast R., Gotthardt P., Luh C. et al. Angiotensin II Receptor 1 Blockage Limits Brain Damage and Improves Functional Outcome After Brain Injury in Aged Animals Despite Age-Dependent Reduction in AT1 Expression. Front Aging Neurosci. 2019; 11: 63. DOI: 10.3389/fnagi.2019.00063
  41. Iovino M., Messana T., De Pergola G. et al. Brain Angiotensinergic Regulation of the Immune System: Implications for Cardiovascular and Neuroendocrine Responses. Endocr Metab Immune Disord Drug Targets. 2020; 20 (1): 15–24. DOI: 10.2174/1871530319666190617160934
  42. Kim M., Bang J., Lee J. et al. Ginkgo biloba L. extract protects against chronic cerebral hypoperfusion by modulating neuroinflammation and the cholinergic system. Phytomedicine. 2016; 23 (12): 1356–64. DOI: 10.1016/j.phymed.2016.07.013
  43. O’Connor A., Clark M. Angiotensin II induces cyclooxygenase 2 expression in rat astrocytes via the angiotensin type 1 receptor. Neuropeptides. 2019; 77: 101958. DOI: 10.1016/j.npep.2019.101958
  44. Mowry F., Biancardi V. Neuroinflammation in hypertension: the renin-angiotensin system versus pro-resolution pathways. Pharmacol Res. 2019; 144: 279–91. DOI: 10.1016/j.phrs.2019.04.029
  45. Don-Doncow N., Vanherle L., Zhang Y. et al. T-cell accumulation in the hypertensive brain: a role for sphingosine-1-phosphate-mediated chemotaxis. Int J Mol Sci. 2019; 20 (3): E537. DOI: 10.3390/ijms20030537
  46. Iulita M., Duchemin S., Vallerand D. et al. CD4+ Regulatory T Lymphocytes Prevent Impaired Cerebral Blood Flow in Angiotensin II-Induced Hypertension. J Am Heart Assoc. 2019; 8 (1): e009372. DOI: 10.1161/JAHA.118.009372