Effect of renin-angiotensin-aldosterone system inhibitors on functional activity of the spinal cord and nerve roots in patients with degenerative lumbar spine diseases

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OBJECTIVE

To evaluate the effect of renin-angiotensin-aldosterone system inhibitors on functional activity of the spinal cord and nerve roots in patients with degenerative lumbar spine diseases.

MATERIAL AND METHODS

A retrospective observational cohort study was performed. We evaluated clinical and radiological parameters (gender, age of patients, type of antihypertensive drug, concomitant diseases, ODI (6) and SF-36 (7) scores of patient quality of life), functional recovery, increase of signal intensity and its area in T2WIs, localization and maximum spinal canal stenosis, as well as maximum spinal cord and nerve root compression.

RESULTS

The study included 117 medical records of respondents (88 men and 29 women aged 56.9±13.2 years) who underwent lumbar spine surgery for degenerative diseases. Arterial hypertension was verified in 68 (58.1%) patients, diabetes mellitus in 22 (18.8%) respondents. Age (p=0.002), diabetes mellitus (p=0.007), arterial hypertension (p=0.015) and antihypertensive therapy (p=0.023) were significantly associated with worse clinical and neurological status of patients. Binary logistic regression model demonstrated that only arterial hypertension was significantly associated with low preoperative quality of life (p=0.002).

CONCLUSION

Intake of AT II-1 receptor blockers and angiotensin converting enzyme inhibitors for arterial hypertension is a significant predictor of decrease in signal intensity of the spinal cord and its roots according to T2WIs.

Keywords:

renin-angiotensin-aldosterone system

angiotensin II

angiotensin II-1 receptor blockers

angiotensin converting enzyme inhibitors

lumbar spine

degenerative diseases

spinal cord

spinal cord roots

functional activity

Authors:

Korolishin V.A.

Burdenko Neurosurgery Center

Stepanov I.A.

Irkutsk State Medical University

ORCID: 0000-0001-9039-9147

beloborodov V.A.

Irkutsk State Medical University

ORCID: 0000-0002-3299-1924

Brinyuk E.S.

Burdenko Neurosurgical Center

ORCID: 0000-0002-0346-8018

Konovalov N.A.

Burdenko Neurosurgical Center

ORCID: 0000-0003-0824-1848

Received:

22.03.2021

Accepted:

05.08.2021

List of references:

Prasad GL, Menon GR. Simple Cost-Effective Surgeries for Degenerative Lumbar Spine Disease. World Neurosurgery. 2017;98:861. https://doi.org/10.1016/j.wneu.2016.08.076
Graham P. Lumbar Degenerative Disease with Intervertebral Disk Herniation. Orthopedic Nursing. 2018;37(1):68-69. https://doi.org/10.1097/NOR.0000000000000427
Wang JC, Dailey AT, Mummaneni PV, Ghogawala Z, Resnick DK, Watters WC, Groff MW, Choudhri TF, Eck JC, Sharan A, Dhall SS, Kaiser MG. Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 8: lumbar fusion for disc herniation and radiculopathy. Journal of Neurosurgery. Spine. 2014;21(1):48-53. https://doi.org/10.3171/2014.4.SPINE14271
Keorochana G, Setrkraising K, Woratanarat P, Arirachakaran A, Kongtharvonskul J. Clinical outcomes after minimally invasive transforaminal lumbar interbody fusion and lateral lumbar interbody fusion for treatment of degenerative lumbar disease: a systematic review and meta-analysis. Neurosurgical Review. 2018;41(3):755-770. https://doi.org/10.1007/s10143-016-0806-8
Jensen MC, Kelly AP, Brant-Zawadzki MN. MRI of degenerative disease of the lumbar spine. Magnetic Resonance Quarterly. 1994;10(3):173-190.
Karsy M, Bisson EF. Surgical Versus Nonsurgical Treatment of Lumbar Spondylolisthesis. Neurosurgery Clinics of North America. 2019;30(3):333-340. https://doi.org/10.1016/j.nec.2019.02.007
Sandrow-Feinberg HR, Houlé JD. Exercise after spinal cord injury as an agent for neuroprotection, regeneration and rehabilitation. Brain Research. 2015;1619:12-21. https://doi.org/10.1016/j.brainres.2015.03.052
Sulejczak D, Taraszewska A, Chrapusta SJ, Dziewulska D, Nakielski P, Rafałowska J. Nanofiber mat spinal cord dressing-released glutamate impairs blood-spinal cord barrier. Folia Neuropathologica. 2016;54(4):392-404. https://doi.org/10.5114/fn.2016.64818
Nishimura Y, Ito T, Saavedra JM. Angiotensin II AT(1) blockade normalizes cerebrovascular autoregulation and reduces cerebral ischemia in spontaneously hypertensive rats. Stroke. 2000;31(10):2478-2486. https://doi.org/10.1161/01.str.31.10.2478
Güler A, Sahin MA, Ucak A, Onan B, Inan K, Oztaş E, Arslan S, Uysal B, Demirkiliç U, Tatar H. Protective effects of angiotensin II type-1 receptor blockade with olmesartan on spinal cord ischemia-reperfusion injury: an experimental study on rats. Annals of Vascular Surgery. 2010;24(6):801-808. https://doi.org/10.1016/j.avsg.2010.03.023
Lin CM, Tsai JT, Chang CK, Cheng JT, Lin JW. Development of telmisartan in the therapy of spinal cord injury: pre-clinical study in rats. Drug Design, Development and Therapy. 2015;9:4709-4717. https://doi.org/10.2147/DDDT.S86616
Kobalava ZhD, Konradi AO, Nedogoda SV, Arutyunov GP, Baranova EI, Barbarash OL, Villeval’de SV, Galyavich AS, Glezer MG, Drapkina OM, Kotovskaya YuV, Libis RA, Lopatin YuM, Nedoshivin AO, Ostroumova OD, Ratova LG, Tkacheva ON, Chazova IE, Chesnikova AI, Chumakova GA. Memorandum of experts of the Russian Society of Cardiology on the recommendations of the European Society of Cardiology/The European Society for Arterial Hypertension for the treatment of arterial hypertension in 2018. Rossijskij kardiologicheskij zhurnal. 2018;23(12):131-142. (In Russ.). https://doi.org/10.15829/1560-4071-2018-12-131-142
von Elm E, Altman DG, Egger M, Stuart JP, Peter CG, Jan PV, STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. International Journal of Surgery. 2014;12(12):1495-1499. https://doi.org/10.1016/j.ijsu.2014.07.013
Skierka AS, Michels KB. Ethical principles and placebo-controlled trials — interpretation and implementation of the Declaration of Helsinki’s placebo paragraph in medical research. BMC Medical Ethics. 2018;19(1):24. https://doi.org/10.1186/s12910-018-0262-9
Belousov YuB. Klinicheskaya farmakologiya: nacional’noe rukovodstvo. Pod red. Belousova Yu.B., Kukesa V.G., Lepahina V.K., Petrova V.I. M.: GEOTAR-Media; 2014. (In Russ.).
Peart WS. Renin-Angiotensin system. Quarterly Journal of Experimental Physiology. 1982;67(3):401-406. https://doi.org/10.1113/expphysiol.1982.sp002655
Navar LG, Nishiyama A. Intrarenal formation of angiotensin II. Contributions to Nephrology. 2001;135:1-15. https://doi.org/10.1159/000060154
Volicer L. Angiotensin. Ceskoslovenska Farmacie. 1965;14(8):431-437.
von Bohlen und Halbach O. Angiotensin IV in the central nervous system. Cell and Tissue Research. 2003;311(1):1-9. https://doi.org/10.1007/s00441-002-0655-3
Ganten D, Speck G. The brain renin-angiotensin system: a model for the synthesis of peptides in the brain. Biochemical Pharmacology. 1978;27(20):2379-2389. https://doi.org/10.1016/0006-2952(78)90348-9
Huber G, Schuster F, Raasch W. Brain renin-angiotensin system in the pathophysiology of cardiovascular diseases. Pharmacological Research. 2017;125(Pt A):729-730. https://doi.org/10.1016/j.phrs.2017.06.016
Farag E, Sessler DI, Ebrahim Z, Kurz A, Morgan J, Ahuja S, Maheshwari K, John Doyle D. The renin angiotensin system and the brain: New developments. Journal of Clinical Neuroscience. 2017;46:1-8. https://doi.org/10.1016/j.jocn.2017.08.055
Villapol S, Saavedra JM. Neuroprotective effects of angiotensin receptor blockers. American Journal of Hypertension. 2015;28(3):289-299. https://doi.org/10.1093/ajh/hpu197
Mehalic TF, Pezzuti RT, Applebaum BI. Magnetic resonance imaging and cervical spondylotic myelopathy. Neurosurgery. 1990;26(2):217-227. https://doi.org/10.1097/00006123-199002000-00006
Karadimas SK, Moon ES, Yu WR, Satkunendrarajah K, Kallitsis JK, Gatzounis G, Fehlings MG. A novel experimental model of cervical spondylotic myelopathy (CSM) to facilitate translational research. Neurobiology of Disease. 2013;54:43-58. https://doi.org/10.1016/j.nbd.2013.02.013
Karadimas SK, Klironomos G, Papachristou DJ, Papanikolaou S, Papadaki E, Gatzounis G. Immunohistochemical profile of NF-κB/p50, NF-κB/p65, MMP-9, MMP-2, and u-PA in experimental cervical spondylotic myelopathy. Spine. 2013;38(1):4-10. https://doi.org/10.1097/BRS.0b013e318261ea6f
Perdomo-Pantoja A, Chara A, Kalb S, Casaos J, Ahmed AK, Pennington Z, Cottrill E, Shah S, Jiang B, Manbachi A, Zygourakis C, Witham TF, Theodore N. The effect of renin-angiotensin system blockers on spinal cord dysfunction and imaging features of spinal cord compression in patients with symptomatic cervical spondylosis. The Spine Journal. 2020;20(4):519-529. https://doi.org/10.1016/j.spinee.2019.12.002
Fleegal-DeMotta MA, Doghu S, Banks WA. Angiotensin II modulates BBB permeability via activation of the AT(1) receptor in brain endothelial cells. Journal of Cerebral Blood Flow and Metabolism. 2009;29(3):640-647. https://doi.org/10.1038/jcbfm.2008.158
Sano H, Hosokawa K, Kidoya H, Takakura N. Negative regulation of VEGF-induced vascular leakage by blockade of angiotensin II type 1 receptor. Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26(12):2673-2680. https://doi.org/10.1161/01.ATV.0000245821.77155.c3
Lucius R, Gallinat S, Rosenstiel P, Herdegen T, Sievers J, Unger T. The angiotensin II type 2 (AT2) receptor promotes axonal regeneration in the optic nerve of adult rats. The Journal of Experimental Medicine. 1998;188(4):661-670. https://doi.org/10.1084/jem.188.4.661
Reinecke K, Lucius R, Reinecke A, Rickert U, Herdegen T, Unger T. Angiotensin II accelerates functional recovery in the rat sciatic nerve in vivo: role of the AT2 receptor and the transcription factor NF-kappaB. FASEB Journal. 2003;17(14):2094-2096. https://doi.org/10.1096/fj.02-1193fje
Li ZQ, Zhao YP, Jia WY, Wang X, Chen B, Shahbaz M, Nie L, Cheng L. Surgical Treatment of Cervical Spondylotic Myelopathy Associated Hypertension — A Retrospective Study of 309 Patients. PLoS One. 2015;10(7):e0133828. https://doi.org/10.1371/journal.pone.0133828
Peng B, Pang X, Li D, Yang H. Cervical spondylosis and hypertension: a clinical study of 2 cases. Medicine. 2015;94(10):e618. https://doi.org/10.1097/MD.0000000000000618
Itoki K, Kurokawa R, Shingo T, Kim P. Effect of Myoarchitectonic Spinolaminoplasty on Concurrent Hypertension in Patients with Cervical Spondylotic Myelopathy. Neurospine. 2018;15(1):77-85. https://doi.org/10.14245/ns.1836020.010

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