Reproductive Immunology: Open Access

Introduction

Research that has led to Immune System participation in the pathology of Hypertension is relatively new. Association between HTA and renal disease was reported on 1879 [1] and the first description of autoimmunity as producing morbid situation appeared on 1904 when the antibodies description causing hemolytic anemia in the crio haemoglobin paroxysmic [2] where the end of the stated situation by Paul Erlich who established that the organism didn’t hurt himself (horror autotoxicus) [3].

Pioneer observations about participation in experimental models in HTA started to re appear at the end of the last century [4], however it has been in the last few decades when an increasingly number of researches [5] have led to establish in an unmistakable manner the critical role of autoimmunity in the complex etic pathogenic mechanism which results in the elevation of HTA [6-9].

Inflammation as Manifestation of the Immune Reactivity of Hypertension Arterial

Inflammation as a demonstration of the immune reactivity of Hypertension Arterial. It is very well stablished that the kidneys inflammation, in the arterial wall and the central nervous system helps development and increases severity of the hypertension. The potential hypertensive of the inflammation in these target organs has been demonstrated in the studies in which the inflammation has been reduced with a range of immune suppressor’s treatments which result in the prevention or improvement of hypertension in practically all of the hyper tense ceps of mice. Even more, the experimental induction of the renal inflammation is associated with the increase of the arterial hypertension [7].

Renal inflammation induces hypertension as a result of the reduction of the natriuretic by pressure, which is the response of the renal adaptation to a sodium positive balance. The reduction of the natriuretic response by the increase of the pressure of renal perfusion which is caused by the tubulointerstitial inflammation of the release of oxidative stress with reduce of nitric oxide, increase of the angiotensin activity and the effects profibrotic with losses peritubular capillary. In the arterial wall, inflammation increases the local produce of reactive species of oxygen, increases the vasoconstrictor tone and suppresses the endothelial vasodilatation response. In the central nervous system, the inflammation of the areas in the third ventriculus helps lymphocyte migration to the arterial wall (originator of the vascular inflammation) and stimulates the activity of the sympathetic nervous system which carries not only the increase of the vasoconstrictor tone, cardiac expense and the reabsorption tubular of sodium, but also, induces the stimulation of various aspects of the immune system.

Lymphocytes Participation in the Pathology of Hypertension Arterial

Lymphocytes paper in the pathology of hypertension was initially found in pioneer experiments of Svendsen [4], who demonstrated that the malnourished mouse didn’t develop hypertension depending of salt in the model DOCA (deoxycorticosterone). Hypertension development capacity in this phase of the experimental model was recovered with the lymphocytes transfer. Guzik et al. [10] demonstrated that induced hypertension by angiotensin II was surprised in mice Rag 1-/-, lacking lymphocytes, and that the response to angiotensin was restored with the adoptive transfer of lymphocytes T. same resistance to hypertension was demonstrated in mice Dahl nulls for Rag 1. [11]. Lymphocytes B paper was demonstrated by Chan et al. [12], who used mice BAFFR -/- (lacking B cell activation factor receiver).

Lymphocytes Participation in the Pathology of Hypertension Arterial

Lymphocytes paper in the pathology of hypertension was initially found in pioneer experiments of Svendsen [4], who demonstrated that the malnourished mouse didn’t develop hypertension depending of salt in the model DOCA (deoxycorticosterone). Hypertension development capacity in this phase of the experimental model was recovered with the lymphocytes transfer. Guzik et al. [10] demonstrated that induced hypertension by angiotensin II was surprised in mice Rag 1-/-, lacking lymphocytes, and that the response to angiotensin was restored with the adoptive transfer of lymphocytes T. same resistance to hypertension was demonstrated in mice Dahl nulls for Rag 1. [11]. Lymphocytes B paper was demonstrated by Chan et al. [12], who used mice BAFFR -/- (lacking B cell activation factor receiver).

Inherent Immunity, Acquired and Autoimmunity in Hypertension Arterial

Inherited immunity, acquired immunity and autoimmunity have a real important role in hypertension arterial. There is evidence that the activation of inflammasome NLPR3 in induced hypertension by salt [13] and in other hypertension experimental types. In hypertension patients has been evidence demonstrated of activation of inherited immunity, including increase of the receptors toll like (TLR) 2 and 4 in monocytes of peripheral blood and increase in plasmatic levels of IL-1 Beta and of IL-18 [14-16].

All aspects of immunity acquired have been demonstrated in experimental types of hypertension, including incorporated antigens in cells presenting antigen in situ and circulating, coestimulation and cell T release of immune memory [17-19]. In patients with essential hypertension have been detected antibodies directed to antigens of pathological potential [20,21].

Even the hypertensive patient doesn’t have hypernatremia, increase of concentration of sodium inside the range do not exceed physiological levels is able to polarized T cell indifferent towards generation of IL-17 cells through activation of SGK1 (serum and glucocorticoid regulated kinase 1) [22-24]. Generation of IL-17 helps autoimmunity, inflammation and over regulated cotrasporter Na-K-2CL.

The importance of IL-17 generation by increase of the sodium concentration must be considered in the context of increase levels chronic in the concentration of sodium (≥ 3 mMol/L) which stimulate the central nervous system and increase the arterial pressure [25].

On the other hand, overload sodium causes high concentration in subcutaneous tissue led to glycosaminoglycans. This tissular increase of sodium, without systemic repercussion, induces stimulation of TonEBP (tonicityresponsive enhancer binding protein) which increases infiltration of macrophages with generation of VEGF-C (vascular endothelial growth factor-C) and increase in the subcutaneous lymphatic network [26] Subcutaneous levels of sodium in these conditions are inside range which could help generate IL-17 [22,23].

Autoantigens which evidence base experimental is being object in human studies are modified proteins by generation of isoketales which result in peroxidation of lipids and stress proteins 70 (HSP70) [17,27]. Participation of the last one can be induced by over expression and mobilization to extracellular space or make its protection function and antigen transport to major complex of histocompatibility of cells with antigen [28].

A Look towards the Future

Possibility of eliminate or avoid lead elements of the immune reactivity with the objective of prevent or treat hypertension arterial is subject to identification of factors that most likely are multiple and variable in different habitats, groups of different age and different sex. Potential antigen assessment and its generation pathologist and physiologist are a great part of current research about immune pathology of hypertension and they promise results in the near future.

Discussion

On the other hand, possibility of an immunosuppression being a valid therapeutic option in resistant severe hypertension to treatment needs to be explored. Various studies have shown high levels of cytosine’s in hypertensive patients, and, recently Chen at al. [29] assessed a reasonable number of patients with renal insufficiency who had resistant hypertension and they found an important increase of TNF α and IL-6 and reduction of TGF β levels In studies of 6-7 years following those patients they had an increase in mortality and cardiovascular diseases. Recently, it has been highlighted in an editorial [30], these results open the option to use treatment of anti-IL-6 o antiTNF αThere is a report of a short treatment course with mycophenolate mofetil which resulted in change of severe hypertension resistant to treatment in a patient with easy control [31].

Conclusion

There is the need of meticulous studies which can clarify the clinical characteristics and the values of cytosines which can allow predicting a potential good result of the immunosuppression in transitory essential hypertension.

Acknowledgement

Researchers appreciate all the participants in this study for their cooperation during the data collection periods.

Conflict of Interest

Author has no conflict of Interest.

References

1. Mahomed FA (1879) On chronic Brightâ??s disease and its essential symptoms. Lancet 113: 399-401.
2. Donath J, Landsteiner K (1904) �ber paroxysmale Hämoglobinurie. Münch med Wochenschr 51: 1590-601.
3. Ehrlich P, Morgenroth J, Berlin klin Wochenschr (1901) Reproducida en inglés en Ehrlich P 38 251-257. The Collected Papers of Paul Erlich. 1957; note 2(II):253 Pergamon Press NY.
4. Svendsen UG (1975) Studies elucidating the importance of thymus on the degree of increased blood pressure and vascular 3 disease in renal hypertensive mice. A comparison of the disease in nude and haired littermates. Acta Pathol Microbiol Scand 83: 568-72.
5. Ryan MJ (2013) Immune mechanisms in hypertension. En: Granger ND, Granger J, editores. En: Colloquium Series on Integrated system Physiology. Clayp Lif Scie 33-44.
6. Norlander AE, Madhur MS, Harrison DG (2018) The immunology of hypertension. J Exp Med 215: 21-33.
7. Rodriguez-Iturbe B, Pons H, Johnson RJ (2017) Role of the immune system in hypertension. Physiol Rev 97: 1127-64.
8. Abais-Battad JM, Dasinger JH, Fehrenbach DJ, Mattson DL (2017) Novel adaptive and innate immunity targets in hypertension. Pharmacol Res 120: 109-15.
9. Guyton AC, Coleman TG, Cowley AV Jr, Scheel KW, Manning RD Jr, et al. (1972) Arterial pressure regulation overriding dominance of the kidneys in long-term regulation and in hypertension. Am J Med 52: 584-94.
10. Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, et al. (2007) Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med 204: 2449-60.
11. Mattson DL, Lund H, Guo C, Rudemiller N, Geurts AM, et al. (2013) Genetic mutation of recombination activating gene 1 in Dahl salt-sensitive rats attenuates hypertension and renal damage. Am J Physiol Regul Integr Comp Physiol 304: 407-14.
12. Chan CT, Sobey CG, Lieu M, Ferens D, Kett MM, et al. (2015) Obligatory role for B cells in the development of angiotensin II-dependent hypertension. Hyperte 66: 1023-33.
13. Liu D, Zeng X, Li X, Mehta JL, Wang X (2017)Role of NLRP3 inflammasome in the pathogenesis of cardiovascular diseases. Basic Res Cardiol 113: 5.
14. Marketou ME, Kontaraki JE, Zacharis EA, Kochiadakis GE, Giaouzaki A, et al. (2012) TLR2 and TLR4 gene expression in peripheral monocytes in nondiabetic hypertensive patients: The effect of intensive blood pressure-lowering. J Clin Hypertens 14: 330-5.
15. Zirlik A, Abdullah SM, Gerdes N, MacFarlane L, Schönbeck U, et al. (2007) Interleukin-18, the metabolic syndrome, and subclinical atherosclerosis: Results from the Dallas Heart Study. Arterioscler Thromb Vasc Biol 27: 2043-9.
16. Blankenberg S, Luc G, Ducimetière P, Arveiler D, Ferrières J, et al. (2003) PRIME Study Group Interleukin-18 and the risk of coronary heart disease in European men: The Prospective Epidemiological Study of Myocardial Infarction (PRIME). Circulati 108: 2453-9.
17. Kirabo A, Fontana V, de Faria AP, Loperena R, Galindo CL, et al. (2014) DC isoketal-modified proteins activate T cells and promote hypertension. J Clin Invest 124: 4642-56.
18. Vinh A, Chen W, Blinder Y, Weiss D, Taylor WR, et al. (2010) Inhibition and genetic ablation of the B7/CD28 T-cell costimulation axis prevents experimental hypertension. Circulat 122: 2529-37.
19. Itani HA, Xiao L, Saleh MA, Wu J, Pilkinton MA, et al. (2016) CD70 exacerbates blood pressure elevation and renal damage in response to repeated hypertensive stimuli. Circ Res 118: 1233-43.
20. Pockley AG, de Faire U, Kiessling R, Lemne C, Thulin T, et al. (2002) Circulating heat shock protein and heat shock protein antibody levels in established hypertension. J Hypertens 20: 1815-20.
21. Wu T, Ma J, Chen S, Sun Y, Xiao C (2001)Association of plasma antibodies against the inducible Hsp70 with hypertension and harsh working conditions. Cel StreChapero 6: 394-401.
22. Wu C, Yosef N, Thalhamer T, Zhu C, Xiao S, et al. (2013) Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Natu 496: 513-7.
23. Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, et al. (2013) Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Natu 496: 518-22.
24. Norlander AE, Saleh MA, Pandey AK, Itani HA, Wu J (2017)A salt-sensing kinase in T lymphocytes SGK1, drives hypertension and hypertensive end-organ damage. JCI Insight 2: e92801,
25. Oâ??Dounaughy TL, Brooks VL (2006) Deoxycorticosterone acetate-salt rats: Hypertension and sympathoexcitation driven by increased NaCl levels. Hyperte 47: 680-5.
26. Wiig H, Schröder A, Neuhofer W, Jantsch J, Kopp C, et al. (2013) Immune cells control skin lymphatic electrolyte homeostasis and blood pressure. J Clin Invest 123: 2803-15.
27. Pons H, Ferrebuz A, Quiroz Y, Romero-Vasquez F, Parra G, et al. (2013) Immune reactivity to heat shock protein 70 expressed in the kidney is cause of salt sensitive hypertension. Am J Physiol Renal Physiol 304: F289-99.
28. Rodriguez-Iturbe B, Lanaspa M, Johnson RJ (2018) The role of autoimmune reactivity induced by heat shock protein 70 in the pathogenesis of essential hypertension. Brit J Pharmacol 176: 1829-1838.
29. Chen J, Bundy JD, Hamm Hsu CY, Lash J, Miller ER (2019) 3rd. Inflammation and apparent treatment resistant-hypertension in patients with chronic kidney disease: The results from the CRIC study. Hyperte 73: 785-93.
30. Barbaro NR, Harrison DG (2019) Markers or makers: Inflammatory cytokines in treatment-resistant hypertension. Hyperten 73: 767-9.
31. Rodriguez-Iturbe B (2016) Autoimmunity in the pathogenesis of hypertension. Hyperten 67:477-83.