Skip to main content

Advertisement

SpringerLink
Log in

Vascular function and multiple sclerosis

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Multiple sclerosis (MS) is a debilitating disease with an assumed autoimmune etiology which may lead to elevated oxidative stress, vascular dysfunction, and subsequent predisposition to cardiovascular disease. Therefore, the primary aim of this study was to evaluate vascular function and the potential role of oxidative stress in patients diagnosed with MS compared to healthy controls (C). Fourteen patients with relapsing–remitting MS (47 ± 3 years) and 13 age- and activity-matched controls (44 ± 5 years) underwent brachial artery flow-mediated dilation (FMD) and reactive hyperemia testing using ultrasound Doppler. Venous blood was analyzed for C-reactive protein (CRP), lipid hydroperoxides (LH), the ferric reducing ability of plasma (FRAP), superoxide dismutase (SOD), and catalase activity. CRP [1.8 ± 0.5 mg/L (MS), 1.0 ± 0.5 mg/L (C)] and LH [1.2 ± 0.2 μmol/L (MS), 1.1 ± 0.1 μmol/L (C)] were not different between MS patients and controls. FMD [8.0 ± 1.2% (MS) and 9.2 ± 1.6% (C)] and reactive hyperemia [380 ± 61 mL (MS) and 402 ± 69 mL (C)] were also not different between groups. Vascular function, as assessed by both FMD and reactive hyperemia, was not impaired in patients with MS compared to controls. Further, there was no evidence of elevated systemic inflammation or oxidative stress in these patients, who were currently all in remission. These findings suggest that impaired vascular function, elevated inflammation and oxidative stress are not an obligatory accompaniment to MS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Soilu-Hanninen M, Koskinen JO, Laaksonen M, Hanninen A, Lilius EM, Waris M (2005) High sensitivity measurement of CRP and disease progression in multiple sclerosis. Neurology 65:153–155

    Article  PubMed  CAS  Google Scholar 

  2. Lilius EM, Rose JW (2006) Antioxidants in multiple sclerosis: do they have a role in therapy? CNS Drugs 20(6):433–441

    Article  Google Scholar 

  3. Gabay C, Kushner I (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340(6):448–454

    Article  PubMed  CAS  Google Scholar 

  4. Del Rincon I, Williams K, Stern M, Freeman GL, O’Leary DH (2003) Escalante A: association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. Arthritis Rheum 48:1833–1840

    Article  PubMed  Google Scholar 

  5. Duprez DA, Somasundaram PE, Sigurdsson G, Hoke L, Florea N, Cohn JN (2005) Relationship between C-reactive protein and arterial stiffness in an asymptomatic population. J Hum Hypertens 19:515–519

    Article  PubMed  CAS  Google Scholar 

  6. Wong M, Toh L, Wilson A, Rowley K, Karschimkus C, Prior D, Romas E, Clemens L, Dragicevic G, Harianto H et al (2003) Reduced arterial elasticity in rheumatoid arthritis and the relationship to vascular disease risk factors and inflammation. Arthritis Rheum 48:81–89

    Article  PubMed  Google Scholar 

  7. Giovannoni G, Miller DH, Losseff NA, Lewellyn-Smith N, Thompson AJ, Thompson EJ (2001) Serum inflammatory markers and clinical/MRI markers of disease progression in multiple sclerosis. J Neurol 248:487–495

    Article  PubMed  CAS  Google Scholar 

  8. Ortiz GG, Macias-Islas MA, Pacheco-Moises FP, Cruz-Ramos JA, Sustersik S, Barba EA, Aguayo A (2009) Oxidative stress is increased in serum from Mexican patients with relapsing–remitting multiple sclerosis. Dis Markers 26(1):35–39

    PubMed  CAS  Google Scholar 

  9. Gilgun-Sherki Y, Melamed E, Offen D (2004) The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol 251(3):261–268

    Article  PubMed  CAS  Google Scholar 

  10. Kos D, Kerckhofs E, Nagels G, D’Hooghe MB, Ilsbroukx S (2008) Origin of fatigue in multiple sclerosis: review of the literature. Neurorehabil Neural Repair 22(1):91–100

    PubMed  CAS  Google Scholar 

  11. Smith C, Hale L, Olson K, Schneiders AG (2009) How does exercise influence fatigue in people with multiple sclerosis? Disabil Rehabil 31(9):685–692

    Article  PubMed  Google Scholar 

  12. Motl RW, Arnett PA, Smith MM, Barwick FH, Ahlstrom B, Stover EJ (2008) Worsening of symptoms is associated with lower physical activity levels in individuals with multiple sclerosis. Mult Scler 14(1):140–142

    Article  PubMed  CAS  Google Scholar 

  13. Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 105:1135–1143

    Article  PubMed  CAS  Google Scholar 

  14. Timmerman GM, Stuifbergin AK (1999) Eating patterns in women with multiple sclerosis. J Neurosci Nurs 31(3):152–158

    Article  PubMed  CAS  Google Scholar 

  15. Marrie RA, Rudick R, Horwitz R, Cutter G, Tyry T, Campagnolo D, Vollmer T (2010) Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology 74(13):1041–1047

    Article  PubMed  CAS  Google Scholar 

  16. Yeboah J, Folsom AR, Burke GL, Johnson C, Polak JF, Post W, Lima JA, Crouse JR, Herrington DM (2009) Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation 120(6):502–509

    Article  PubMed  Google Scholar 

  17. Mitchell GF, Parise H, Vita JA, Larson MG, Warner E, Keaney JF Jr, Keyes MJ, Levy D, Vasan RS, Benjamin EJ (2004) Local shear stress and brachial artery flow-mediated dilation: the Framingham Heart Study. Hypertension 44(2):134–139

    Article  PubMed  CAS  Google Scholar 

  18. Harris RA, Nishiyama SK, Wray DW (2010) Richardson RS: ultrasound assessment of flow-mediated dilation. Hypertension 55:1075–1085

    Article  PubMed  CAS  Google Scholar 

  19. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340(8828):1111–1115

    Article  PubMed  CAS  Google Scholar 

  20. Gokce N, Vita JA, Bader DS, Sherman DL, Hunter LM, Holbrook M, O’Malley C, Keaney JF Jr, Balady GJ (2002) Effect of exercise on upper and lower extremity endothelial function in patients with coronary artery disease. Am J Cardiol 90(2):124–127

    Article  PubMed  Google Scholar 

  21. Hoidal JR (2001) Reactive oxygen species and cell signaling. Am J Respir Cell Mol Biol 25(6):661–663

    PubMed  CAS  Google Scholar 

  22. Knowles RG, Moncada S (1994) Nitric oxide synthases in mammals. Biochem J 298(Pt 2):249–258

    PubMed  CAS  Google Scholar 

  23. Gonzalez-Juanatey C, Llorca J, Vazquez-Rodriguez TR, Diaz-Varela N, Garcia-Quiroga H, Gonzalez-Gay MA (2008) Short-term improvement of endothelial function in rituximab-treated rheumatoid arthritis patients refractory to tumor necrosis factor alpha blocker therapy. Arthritis Rheum 59(12):1821–1824

    Article  PubMed  CAS  Google Scholar 

  24. Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33(11):1444–1452

    PubMed  CAS  Google Scholar 

  25. Williams MR, Westerman RA, Kingwell BA, Paige J, Blombery PA, Sudhir K, Komesaroff PA (2001) Variations in endothelial function and arterial compliance during the menstrual cycle. J Clin Endocrinol Metab 86(11):5389–5395

    Article  PubMed  CAS  Google Scholar 

  26. Richardson RS, Donato AJ, Uberoi A, Wray DW, Lawrenson L, Nishiyama S, Bailey DM (2007) Exercise-induced brachial artery vasodilation: role of free radicals. Am J Physiol Heart Circ Physiol 292(3):H1516–H1522

    Article  PubMed  CAS  Google Scholar 

  27. Pyke KE, Tschakovsky ME (2005) The relationship between shear stress and flow-mediated dilation: implications for the assessment of endothelial function. J Physiol 568:357–369

    Article  PubMed  CAS  Google Scholar 

  28. Fukuzawa K, Shibata A, Okamura C, Fujiwara Y, Akai K, Tsuchiya K, Tokumura A, Gebicki JM (2009) Measurement of lipid hydroperoxides by the ferric-xylenol orange method (1) characteristics of the ferric-xylenol orange/membrane phosphatidylcholine complex. J Nutr Sci Vitaminol (Tokyo) 55(1):9–14

    Article  CAS  Google Scholar 

  29. Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239(1):70–76

    Article  PubMed  CAS  Google Scholar 

  30. Freedson PS, Melanson E, Sirard J (1998) Calibration of the computer science and applications, Inc. accelerometer. Med Sci Sports Exerc 30(5):777–781

    Article  PubMed  CAS  Google Scholar 

  31. Vickrey BG, Hays RD, Harooni R, Myers LW, Ellison GW (1995) A health-related quality of life measure for multiple sclerosis. Qual Life Res 4(3):187–206

    Article  PubMed  CAS  Google Scholar 

  32. Uehata A, Lieberman EH, Gerhard MD, Anderson TJ, Ganz P, Polak JF, Creager MA, Yeung AC (1997) Noninvasive assessment of endothelium-dependent flow-mediated dilation of the brachial artery. Vasc Med 2(2):87–92

    PubMed  CAS  Google Scholar 

  33. Khurana SR, Bamer AM, Turner AP, Wadhwani RV, Bowen JD, Leipertz SL, Haselkorn JK (2009) The prevalence of overweight and obesity in veterans with multiple sclerosis. Am J Phys Med Rehabil 88(2):83–91

    Article  PubMed  Google Scholar 

  34. Van Doornum S, McColl G, Jenkins A, Green DJ, Wicks IP (2003) Screening for atherosclerosis in patients with rheumatoid arthritis: comparison of two in vivo tests of vascular function. Arthritis Rheum 48(1):72–80

    Article  PubMed  Google Scholar 

  35. Moro L, Pedone C, Scarlata S, Malafarina V, Fimognari F, Antonelli-Incalzi R (2008) Endothelial dysfunction in chronic obstructive pulmonary disease. Angiology 59(3):357–364

    Article  PubMed  CAS  Google Scholar 

  36. Loscalzo J, Vita JA (1994) Ischemia, hyperemia, exercise, and nitric oxide. Complex physiology and complex molecular adaptations. Circulation 90(5):2556–2559

    PubMed  CAS  Google Scholar 

  37. Huang AL, Silver AE, Shvenke E, Schopfer DW, Jahangir E, Titas MA, Shpilman A, Menzoian JO, Watkins MT, Raffetto JD et al (2007) Predictive value of reactive hyperemia for cardiovascular events in patients with peripheral arterial disease undergoing vascular surgery. Arterioscler Thromb Vasc Biol 27(10):2113–2119

    Article  PubMed  CAS  Google Scholar 

  38. Karg E, Klivenyi P, Nemeth I, Bencsik K, Pinter S, Vecsei L (1999) Nonenzymatic antioxidants of blood in multiple sclerosis. J Neurol 246(7):533–539

    Article  PubMed  CAS  Google Scholar 

  39. Crayton H, Heyman RA, Rossman HS (2004) A multimodal approach to managing the symptoms of multiple sclerosis. Neurology 63(11 Suppl 5):S12–S18

    PubMed  Google Scholar 

  40. Motl RW, McAuley E, Snook EM (2005) Physical activity and multiple sclerosis: a meta-analysis. Mult Scler 11(4):459–463

    Article  PubMed  Google Scholar 

  41. Bencsik K, Rajda C, Fuvesi J, Klivenyi P, Jardanhazy T, Torok M, Vecsei L (2001) The prevalence of multiple sclerosis, distribution of clinical forms of the disease and functional status of patients in Csongrad County, Hungary. Eur Neurol 46(4):206–209

    Article  PubMed  CAS  Google Scholar 

  42. Turner AP, Kivlahan DR, Haselkorn JK (2009) Exercise and quality of life among people with multiple sclerosis: looking beyond physical functioning to mental health and participation in life. Arch Phys Med Rehabil 90(3):420–428

    Article  PubMed  Google Scholar 

  43. Mostert S, Kesselring J (2002) Effects of a short-term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis. Mult Scler 8:161–168

    Article  PubMed  CAS  Google Scholar 

  44. Schapiro RT (2005) Managing symptoms of multiple sclerosis. Neurol Clin 23(1):177–187 (vii)

    Article  PubMed  Google Scholar 

  45. Taddei S, Galetta F, Virdis A, Ghiadoni L, Salvetti G, Franzoni F, Giusti C, Salvetti A (2000) Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes. Circulation 25:2896–2901

    Google Scholar 

Download references

Acknowledgments

The authors thank the subjects for their time and effort in participating in this research study. This study was supported in part by NIH (P01HL091830 RSR) and AHA (0835209 N DWW).

Conflict of interest

There are no conflicts of interest to report.

Author information

Authors and Affiliations

  1. Division of Geriatrics, Department of Internal Medicine, George E. Whalen VA Medical Center, University of Utah, 500 Foothill Drive, Salt Lake City, UT, 84148, USA

    Anette S. Fjeldstad, Jia Zhao, D. Walter Wray & Russell S. Richardson

  2. Geriatric Research, Education, and Clinical Center, VAMC, Salt Lake City, UT, USA

    John McDaniel, D. Walter Wray & Russell S. Richardson

  3. Department of Exercise and Sports Science, University of Utah, Salt Lake City, UT, USA

    Melissa A. H. Witman, Steve J. Ives, James Hannon, D. Walter Wray & Russell S. Richardson

  4. Neurovirology Research Laboratory, VASLCHSC, and Department of Neurology, University of Utah, Salt Lake City, UT, USA

    John W. Rose

  5. The Brain Institute, University of Utah, Salt Lake City, UT, USA

    John W. Rose

Authors
  1. Anette S. Fjeldstad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John McDaniel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Melissa A. H. Witman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steve J. Ives
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jia Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. John W. Rose
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. James Hannon
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D. Walter Wray
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Russell S. Richardson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anette S. Fjeldstad.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fjeldstad, A.S., McDaniel, J., Witman, M.A.H. et al. Vascular function and multiple sclerosis. J Neurol 258, 2036–2042 (2011). https://doi.org/10.1007/s00415-011-6065-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-011-6065-2

Keywords

Search

Navigation