Skip to main content

Arterial Stiffness and the Brain

  • Chapter
  • First Online:
Hypertension and the Brain as an End-Organ Target

Abstract

In healthy humans, brain perfusion is adequately regulated, minute-to-minute, to match flow and neuronal metabolic demand, while cerebral blood flow (CBF) is maintained somewhat constant in the face of a variable systemic blood pressure between periods of sleep and of high intensity exercise. Vascular wall stiffness may impair CBF in pathological conditions such as hypertension or chronic kidney disease and in physiological condition such as aging. Little is known about changes in intracranial vessels stiffness during aging, hypertension, or chronic kidney disease. Cerebral arteries show an increase, a decrease, or no change in distensibility following the conditions and depending on vessel size. It is also well known that peripheral arteries stiffness may have an impact on CBF and lead to brain damages, the so-called pulse wave encephalopathy. Cerebral vessels are low resistance vessels and the pulse wave is transmitted through capillaries to the venous system. Any increase in pulse wave may thus lead to alteration in the neurovascular unit (endothelial cell/astrocyte/neuron) and brain function. This chapter aims at summarizing our knowledge on the interaction between (peripheral) arteries stiffness and brain. We will first summarize the main characteristics of brain vessels before describing pulse wave encephalopathy and emphasizing the potential role of endothelium in the development of cerebral alterations. As stiffness of peripheral arteries may contribute to chronic hypoperfusion, neuronal death, and the cognitive decline observed in hypertension, chronic kidney disease, and aging, this may open the door for potential treatments of these disorders. Drugs that decrease arterial stiffness may prevent or delay cognitive impairment.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80(4):844–66. doi:10.1016/j.neuron.2013.10.008.

    Article  CAS  PubMed  Google Scholar 

  2. Pase MP, Herbert A, Grima NA, Pipingas A, O’Rourke MF. Arterial stiffness as a cause of cognitive decline and dementia: a systematic review and meta-analysis. Intern Med J. 2012;42(7):808–15. doi:10.1111/j.1445-5994.2011.02645.x.

    Article  CAS  PubMed  Google Scholar 

  3. Pase MP, Pipingas A, Kras M, Nolidin K, Gibbs AL, Wesnes KA, Scholey AB, Stough C. Healthy middle-aged individuals are vulnerable to cognitive deficits as a result of increased arterial stiffness. J Hypertens. 2010;28(8):1724–9. doi:10.1097/HJH.0b013e32833b1ee7.

    Article  CAS  PubMed  Google Scholar 

  4. Rabkin SW. Arterial stiffness: detection and consequences in cognitive impairment and dementia of the elderly. J Alzheimers Dis. 2012;32(3):541–9. doi:10.3233/JAD-2012-120757.

    PubMed  Google Scholar 

  5. Scuteri A, Tesauro M, Appolloni S, Preziosi F, Brancati AM, Volpe M. Arterial stiffness as an independent predictor of longitudinal changes in cognitive function in the older individual. J Hypertens. 2007;25(5):1035–40. doi:10.1097/HJH.0b013e3280895b55.

    Article  CAS  PubMed  Google Scholar 

  6. Triantafyllidi H, Arvaniti C, Lekakis J, Ikonomidis I, Siafakas N, Tzortzis S, Trivilou P, Zerva L, Stamboulis E, Kremastinos DT. Cognitive impairment is related to increased arterial stiffness and microvascular damage in patients with never-treated essential hypertension. Am J Hypertens. 2009;22(5):525–30. doi:10.1038/ajh.2009.35.

    Article  PubMed  Google Scholar 

  7. Waldstein SR, Rice SC, Thayer JF, Najjar SS, Scuteri A, Zonderman AB. Pulse pressure and pulse wave velocity are related to cognitive decline in the Baltimore Longitudinal Study of Aging. Hypertension. 2008;51(1):99–104. doi:10.1161/HYPERTENSIONAHA.107.093674. HYPERTENSIONAHA.107.093674 [pii].

    Article  CAS  PubMed  Google Scholar 

  8. Watson NL, Sutton-Tyrrell K, Rosano C, Boudreau RM, Hardy SE, Simonsick EM, Najjar SS, Launer LJ, Yaffe K, Atkinson HH, Satterfield S, Newman AB. Arterial stiffness and cognitive decline in well-functioning older adults. J Gerontol Ser A, Biol Sci Med Sci. 2011;66(12):1336–42. doi:10.1093/gerona/glr119.

    Article  Google Scholar 

  9. Lakatta EG. The reality of aging viewed from the arterial wall. Artery Res. 2013;7(2):73–80. doi:10.1016/j.artres.2013.01.003.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wang M, Jiang L, Monticone RE, Lakatta EG. Proinflammation: the key to arterial aging. Trends Endocrinol Metab. 2014;25(2):72–9. doi:10.1016/j.tem.2013.10.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Fletcher GF. Exercise in the prevention of stroke. Health Rep. 1994;6(1):106–10.

    CAS  PubMed  Google Scholar 

  12. Katzmarzyk PT, Janssen I. The economic costs associated with physical inactivity and obesity in Canada: an update. Can J Appl Physiol. 2004;29(1):90–115.

    Article  PubMed  Google Scholar 

  13. Larson EB, Wang L, Bowen JD, McCormick WC, Teri L, Crane P, Kukull W. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006;144(2):73–81.

    Article  PubMed  Google Scholar 

  14. Lautenschlager NT, Almeida OP. Physical activity and cognition in old age. Curr Opin Psychiatry. 2006;19(2):190–3. doi:10.1097/01.yco.0000214347.38787.37.

    Article  PubMed  Google Scholar 

  15. Grundy SM, Hansen B, Smith Jr SC, Cleeman JI, Kahn RA. Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. Circulation. 2004;109(4):551–6. doi:10.1161/01.CIR.0000112379.88385.67.

    Article  PubMed  Google Scholar 

  16. Koren-Morag N, Goldbourt U, Tanne D. Relation between the metabolic syndrome and ischemic stroke or transient ischemic attack: a prospective cohort study in patients with atherosclerotic cardiovascular disease. Stroke. 2005;36(7):1366–71. doi:10.1161/01.STR.0000169945.75911.33.

    Article  CAS  PubMed  Google Scholar 

  17. O’Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, Rangarajan S, Islam S, Pais P, McQueen MJ, Mondo C, Damasceno A, Lopez-Jaramillo P, Hankey GJ, Dans AL, Yusoff K, Truelsen T, Diener HC, Sacco RL, Ryglewicz D, Czlonkowska A, Weimar C, Wang X, Yusuf S. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case–control study. Lancet. 2010;376(9735):112–23. doi:10.1016/S0140-6736(10)60834-3.

    Article  PubMed  Google Scholar 

  18. Solfrizzi V, Scafato E, Capurso C, D’Introno A, Colacicco AM, Frisardi V, Vendemiale G, Baldereschi M, Crepaldi G, Di Carlo A, Galluzzo L, Gandin C, Inzitari D, Maggi S, Capurso A, Panza F. Metabolic syndrome and the risk of vascular dementia: the Italian Longitudinal Study on Ageing. J Neurol Neurosurg Psychiatr. 2010;81(4):433–40. doi:10.1136/jnnp.2009.181743.

    Article  PubMed  Google Scholar 

  19. Scuteri A, Cunha PG, Rosei EA, Badariere J, Bekaert S, Cockcroft JR, Cotter J, Cucca F, De Buyzere ML, De Meyer T, Ferrucci L, Franco O, Gale N, Gillebert TC, Langlois M, Laucevicius A, Laurent S, Mattace Raso FU, Morrell CH, Muiesan ML, Munnery MM, Navickas R, Oliveira P, Orru M, Pilia MG, Rietzschel ER, Ryliskyte L, Salvetti M, Schlessinger D, Sousa N, Stefanadis C, Strait J, Van Daele C, Villa I, Vlachopoulos C, Witteman J, Xaplanteris P, Nilsson P, Lakatta EG, Hofman A. Arterial stiffness and influences of the metabolic syndrome: a cross-countries study. Atherosclerosis. 2014;233(2):654–60. doi:10.1016/j.atherosclerosis.2014.01.041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. O’Rourke MF, Safar ME, Dzau V. The cardiovascular continuum extended: aging effects on the aorta and microvasculature. Vasc Med. 2010;15(6):461–8. doi:10.1177/1358863X10382946. 1358863X10382946 [pii].

    Article  PubMed  Google Scholar 

  21. Faraci FM, Heistad DD. Regulation of large cerebral arteries and cerebral microvascular pressure. Circ Res. 1990;66(1):8–17.

    Article  CAS  PubMed  Google Scholar 

  22. Kontos HA, Wei EP, Navari RM, Levasseur JE, Rosenblum WI, Patterson Jr JL. Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol. 1978;234(4):H371–83.

    CAS  PubMed  Google Scholar 

  23. Lee RM. Morphology of cerebral arteries. Pharmacol Ther. 1995;66(1):149–73. 016372589400071A [pii].

    Article  CAS  PubMed  Google Scholar 

  24. Schievink WI. Intracranial aneurysms. N Engl J Med. 1997;336(1):28–40. doi:10.1056/NEJM199701023360106.

    Article  CAS  PubMed  Google Scholar 

  25. Heistad DD. What’s new in the cerebral microcirculation? Landis Award lecture. Microcirculation. 2001;8(6):365–75. doi:10.1038/sj/mn/7800109.

    Article  CAS  PubMed  Google Scholar 

  26. Laman JD, Weller RO. Drainage of cells and soluble antigen from the CNS to regional lymph nodes. J Neuroimmun Pharmacol. 2013;8(4):840–56. doi:10.1007/s11481-013-9470-8.

    Article  Google Scholar 

  27. Iliff JJ, Lee H, Yu M, Feng T, Logan J, Nedergaard M, Benveniste H. Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J Clin Investig. 2013;123(3):1299–309. doi:10.1172/JCI67677.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Carare RO, Hawkes CA, Jeffrey M, Kalaria RN, Weller RO. Review: cerebral amyloid angiopathy, prion angiopathy, CADASIL and the spectrum of protein elimination failure angiopathies (PEFA) in neurodegenerative disease with a focus on therapy. Neuropathol Appl Neurobiol. 2013;39(6):593–611. doi:10.1111/nan.12042.

    Article  CAS  PubMed  Google Scholar 

  29. Armulik A, Genove G, Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell. 2011;21(2):193–215. doi:10.1016/j.devcel.2011.07.001. S1534-5807(11)00269-3 [pii].

    Article  CAS  PubMed  Google Scholar 

  30. Hamilton NB, Attwell D, Hall CN. Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease. Front Neuroenerget. 2010;2, 5. doi:10.3389/fnene.2010.00005.

    Article  Google Scholar 

  31. Yemisci M, Gursoy-Ozdemir Y, Vural A, Can A, Topalkara K, Dalkara T. Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med. 2009;15(9):1031–7. doi:10.1038/nm.2022. nm.2022 [pii].

    Article  CAS  PubMed  Google Scholar 

  32. Attwell D, Buchan AM, Charpak S, Lauritzen M, Macvicar BA, Newman EA. Glial and neuronal control of brain blood flow. Nature. 2010;468(7321):232–43. doi:10.1038/nature09613.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Peppiatt CM, Howarth C, Mobbs P, Attwell D. Bidirectional control of CNS capillary diameter by pericytes. Nature. 2006;443(7112):700–4. doi:10.1038/nature05193. nature05193 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Armulik A, Genove G, Mae M, Nisancioglu MH, Wallgard E, Niaudet C, He L, Norlin J, Lindblom P, Strittmatter K, Johansson BR, Betsholtz C. Pericytes regulate the blood–brain barrier. Nature. 2010;468(7323):557–61. doi:10.1038/nature09522. nature09522 [pii].

    Article  CAS  PubMed  Google Scholar 

  35. Daneman R, Zhou L, Kebede AA, Barres BA. Pericytes are required for blood–brain barrier integrity during embryogenesis. Nature. 2010;468(7323):562–6. doi:10.1038/nature09513. nature09513 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fernandez-Klett F, Offenhauser N, Dirnagl U, Priller J, Lindauer U. Pericytes in capillaries are contractile in vivo, but arterioles mediate functional hyperemia in the mouse brain. Proc Natl Acad Sci USA. 2010;107(51):22290–5. doi:10.1073/pnas.1011321108. 1011321108 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. O’Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005;46(1):200–4. doi:10.1161/01.HYP.0000168052.00426.65.

    Article  PubMed  CAS  Google Scholar 

  38. Faraci FM. Protecting against vascular disease in brain. Am J Physiol Heart Circ Physiol. 2011;300(5):H1566–82. doi:10.1152/ajpheart.01310.2010. ajpheart.01310.2010 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Drouin A, Bolduc V, Thorin-Trescases N, Belanger E, Fernandes P, Baraghis E, Lesage F, Gillis MA, Villeneuve L, Hamel E, Ferland G, Thorin E. Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice. Am J Physiol Heart Circ Physiol. 2011;300(3):H1032–43. doi:10.1152/ajpheart.00410.2010. ajpheart.00410.2010 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Koehler RC, Roman RJ, Harder DR. Astrocytes and the regulation of cerebral blood flow. Trends Neurosci. 2009;32(3):160–9. doi:10.1016/j.tins.2008.11.005. S0166-2236(09)00003-4 [pii].

    Article  CAS  PubMed  Google Scholar 

  41. Dietrich HH, Horiuchi T, Xiang C, Hongo K, Falck JR, Dacey Jr RG. Mechanism of ATP-induced local and conducted vasomotor responses in isolated rat cerebral penetrating arterioles. J Vasc Res. 2009;46(3):253–64. doi:10.1159/000167273. 000167273 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Horiuchi T, Dietrich HH, Hongo K, Dacey Jr RG. Mechanism of extracellular K+-induced local and conducted responses in cerebral penetrating arterioles. Stroke. 2002;33(11):2692–9.

    Article  CAS  PubMed  Google Scholar 

  43. Iadecola C, Yang G, Ebner TJ, Chen G. Local and propagated vascular responses evoked by focal synaptic activity in cerebellar cortex. J Neurophysiol. 1997;78(2):651–9.

    CAS  PubMed  Google Scholar 

  44. Little TL, Beyer EC, Duling BR. Connexin 43 and connexin 40 gap junctional proteins are present in arteriolar smooth muscle and endothelium in vivo. Am J Physiol. 1995;268(2 Pt 2):H729–39.

    CAS  PubMed  Google Scholar 

  45. Ngai AC, Nguyen TS, Meno JR, Britz GW. Postischemic augmentation of conducted dilation in cerebral arterioles. Stroke. 2007;38(1):124–30. doi:10.1161/01.STR.0000252157.93998.47. 01.STR.0000252157.93998.47 [pii].

    Article  PubMed  Google Scholar 

  46. Fujii K, Heistad DD, Faraci FM. Flow-mediated dilatation of the basilar artery in vivo. Circ Res. 1991;69(3):697–705.

    Article  CAS  PubMed  Google Scholar 

  47. Ngai AC, Winn HR. Modulation of cerebral arteriolar diameter by intraluminal flow and pressure. Circ Res. 1995;77(4):832–40.

    Article  CAS  PubMed  Google Scholar 

  48. Dietrich HH, Kajita Y, Dacey Jr RG. Local and conducted vasomotor responses in isolated rat cerebral arterioles. Am J Physiol. 1996;271(3 Pt 2):H1109–16.

    CAS  PubMed  Google Scholar 

  49. Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci. 2004;5(5):347–60. doi:10.1038/nrn1387. nrn1387 [pii].

    Article  CAS  PubMed  Google Scholar 

  50. LaBarbera M. Principles of design of fluid transport systems in zoology. Science. 1990;249(4972):992–1000.

    Article  CAS  PubMed  Google Scholar 

  51. Malek AM, Alper SL, Izumo S. Hemodynamic shear stress and its role in atherosclerosis. JAMA. 1999;282(21):2035–42.

    Article  CAS  PubMed  Google Scholar 

  52. Papaioannou TG, Karatzis EN, Vavuranakis M, Lekakis JP, Stefanadis C. Assessment of vascular wall shear stress and implications for atherosclerotic disease. Int J Cardiol. 2006;113(1):12–8. doi:10.1016/j.ijcard.2006.03.035. S0167-5273(06)00433-5 [pii].

    Article  PubMed  Google Scholar 

  53. Kamiya A, Bukhari R, Togawa T. Adaptive regulation of wall shear stress optimizing vascular tree function. Bull Math Biol. 1984;46(1):127–37.

    Article  CAS  PubMed  Google Scholar 

  54. Langille BL, O’Donnell F. Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science. 1986;231(4736):405–7.

    Article  CAS  PubMed  Google Scholar 

  55. Drouin A, Thorin E. Flow-induced dilation is mediated by Akt-dependent activation of endothelial nitric oxide synthase-derived hydrogen peroxide in mouse cerebral arteries. Stroke. 2009;40(5):1827–33. doi:10.1161/STROKEAHA.108.536805. STROKEAHA.108.536805 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ando J, Yamamoto K. Vascular mechanobiology: endothelial cell responses to fluid shear stress. Circ J. 2009;73(11):1983–92. JST.JSTAGE/circj/CJ-09-0583 [pii].

    Article  CAS  PubMed  Google Scholar 

  57. Rosenblum WI. Is the EDRF in the cerebral circulation NO? Its release by shear and the dangers in interpreting the effects of NOS inhibitors. Keio J Med. 1998;47(3):142–9.

    Article  CAS  PubMed  Google Scholar 

  58. Thorin-Trescases N, Bevan JA. High levels of myogenic tone antagonize the dilator response to flow of small rabbit cerebral arteries. Stroke. 1998;29(6):1194–200. discussion 1200–1191.

    Article  CAS  PubMed  Google Scholar 

  59. Ward ME, Yan L, Kelly S, Angle MR. Flow modulation of pressure-sensitive tone in rat pial arterioles: role of the endothelium. Anesthesiology. 2000;93(6):1456–64.

    Article  CAS  PubMed  Google Scholar 

  60. Golding EM, Marrelli SP, You J, Bryan Jr RM. Endothelium-derived hyperpolarizing factor in the brain: a new regulator of cerebral blood flow? Stroke. 2002;33(3):661–3.

    PubMed  Google Scholar 

  61. You J, Golding EM, Bryan Jr RM. Arachidonic acid metabolites, hydrogen peroxide, and EDHF in cerebral arteries. Am J Physiol Heart Circ Physiol. 2005;289(3):H1077–83. doi:10.1152/ajpheart.01046.2004.

    Article  CAS  PubMed  Google Scholar 

  62. Paravicini TM, Miller AA, Drummond GR, Sobey CG. Flow-induced cerebral vasodilatation in vivo involves activation of phosphatidylinositol-3 kinase, NADPH-oxidase, and nitric oxide synthase. J Cereb Blood Flow Metab. 2006;26(6):836–45. doi:10.1038/sj.jcbfm.9600235. 9600235 [pii].

    Article  CAS  PubMed  Google Scholar 

  63. Koller A, Toth P. Contribution of flow-dependent vasomotor mechanisms to the autoregulation of cerebral blood flow. J Vasc Res. 2012;49(5):375–89. doi:10.1159/000338747.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Bryan Jr RM, Marrelli SP, Steenberg ML, Schildmeyer LA, Johnson TD. Effects of luminal shear stress on cerebral arteries and arterioles. Am J Physiol Heart Circ Physiol. 2001;280(5):H2011–22.

    CAS  PubMed  Google Scholar 

  65. Bryan Jr RM, Steenberg ML, Marrelli SP. Role of endothelium in shear stress-induced constrictions in rat middle cerebral artery. Stroke. 2001;32(6):1394–400.

    Article  CAS  PubMed  Google Scholar 

  66. Madden JA, Christman NJ. Integrin signaling, free radicals, and tyrosine kinase mediate flow constriction in isolated cerebral arteries. Am J Physiol. 1999;277(6 Pt 2):H2264–71.

    CAS  PubMed  Google Scholar 

  67. Shimoda LA, Norins NA, Jeutter DC, Madden JA. Flow-induced responses in piglet isolated cerebral arteries. Pediatr Res. 1996;39(4 Pt 1):574–83. doi:10.1203/00006450-199604000-00002.

    Article  CAS  PubMed  Google Scholar 

  68. Garcia-Roldan JL, Bevan JA. Flow-induced constriction and dilation of cerebral resistance arteries. Circ Res. 1990;66(5):1445–8.

    Article  CAS  PubMed  Google Scholar 

  69. Toth P, Rozsa B, Springo Z, Doczi T, Koller A. Isolated human and rat cerebral arteries constrict to increases in flow: role of 20-HETE and TP receptors. J Cereb Blood Flow Metab. 2011;31:2096–105. doi:10.1038/jcbfm.2011.74. jcbfm201174 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Faraci FM, Heistad DD. Regulation of the cerebral circulation: role of endothelium and potassium channels. Physiol Rev. 1998;78(1):53–97.

    CAS  PubMed  Google Scholar 

  71. Korshunov VA, Schwartz SM, Berk BC. Vascular remodeling: hemodynamic and biochemical mechanisms underlying Glagov’s phenomenon. Arterioscler Thromb Vasc Biol. 2007;27(8):1722–8. doi:10.1161/ATVBAHA.106.129254.

    Article  CAS  PubMed  Google Scholar 

  72. Korshunov VA, Berk BC. Strain-dependent vascular remodeling: the “Glagov phenomenon” is genetically determined. Circulation. 2004;110(2):220–6. doi:10.1161/01.CIR.0000134958.88379.2E.

    Article  PubMed  Google Scholar 

  73. Laurent S, Boutouyrie P. Recent advances in arterial stiffness and wave reflection in human hypertension. Hypertension. 2007;49(6):1202–6. doi:10.1161/HYPERTENSIONAHA.106.076166.

    Article  CAS  PubMed  Google Scholar 

  74. Kwater A, Gasowski J, Gryglewska B, Wizner B, Grodzicki T. Is blood flow in the middle cerebral artery determined by systemic arterial stiffness? Blood Press. 2009;18(3):130–4. doi:10.1080/08037050902975114.

    Article  PubMed  Google Scholar 

  75. Hirata K, Yaginuma T, O’Rourke MF, Kawakami M. Age-related changes in carotid artery flow and pressure pulses: possible implications for cerebral microvascular disease. Stroke. 2006;37(10):2552–6. doi:10.1161/01.STR.0000242289.20381.f4.

    Article  PubMed  Google Scholar 

  76. Henry Feugeas MC, De Marco G, Peretti II, Godon-Hardy S, Fredy D, Claeys ES. Age-related cerebral white matter changes and pulse-wave encephalopathy: observations with three-dimensional MRI. Magn Reson Imaging. 2005;23(9):929–37. doi:10.1016/j.mri.2005.09.002.

    Article  PubMed  Google Scholar 

  77. Kuo HK, Chen CY, Liu HM, Yen CJ, Chang KJ, Chang CC, Yu YH, Lin LY, Hwang JJ. Metabolic risks, white matter hyperintensities, and arterial stiffness in high-functioning healthy adults. Int J Cardiol. 2010;143(2):184–91. doi:10.1016/j.ijcard.2009.02.005.

    Article  PubMed  Google Scholar 

  78. Poels MM, Zaccai K, Verwoert GC, Vernooij MW, Hofman A, van der Lugt A, Witteman JC, Breteler MM, Mattace-Raso FU, Ikram MA. Arterial stiffness and cerebral small vessel disease: the Rotterdam Scan Study. Stroke. 2012;43(10):2637–42. doi:10.1161/STROKEAHA.111.642264.

    Article  PubMed  Google Scholar 

  79. Henskens LH, Kroon AA, van Oostenbrugge RJ, Gronenschild EH, Fuss-Lejeune MM, Hofman PA, Lodder J, de Leeuw PW. Increased aortic pulse wave velocity is associated with silent cerebral small-vessel disease in hypertensive patients. Hypertension. 2008;52(6):1120–6. doi:10.1161/HYPERTENSIONAHA.108.119024.

    Article  CAS  PubMed  Google Scholar 

  80. Kearney-Schwartz A, Rossignol P, Bracard S, Felblinger J, Fay R, Boivin JM, Lecompte T, Lacolley P, Benetos A, Zannad F. Vascular structure and function is correlated to cognitive performance and white matter hyperintensities in older hypertensive patients with subjective memory complaints. Stroke. 2009;40(4):1229–36. doi:10.1161/STROKEAHA.108.532853.

    Article  PubMed  Google Scholar 

  81. van Elderen SG, Brandts A, van der Grond J, Westenberg JJ, Kroft LJ, van Buchem MA, Smit JW, de Roos A. Cerebral perfusion and aortic stiffness are independent predictors of white matter brain atrophy in type 1 diabetic patients assessed with magnetic resonance imaging. Diabetes Care. 2011;34(2):459–63. doi:10.2337/dc10-1446.

    Article  PubMed  PubMed Central  Google Scholar 

  82. van Elderen SG, Brandts A, Westenberg JJ, van der Grond J, Tamsma JT, van Buchem MA, Romijn JA, Kroft LJ, Smit JW, de Roos A. Aortic stiffness is associated with cardiac function and cerebral small vessel disease in patients with type 1 diabetes mellitus: assessment by magnetic resonance imaging. Eur Radiol. 2010;20(5):1132–8. doi:10.1007/s00330-009-1655-4.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Tarumi T, Ayaz Khan M, Liu J, Tseng BM, Parker R, Riley J, Tinajero C, Zhang R. Cerebral hemodynamics in normal aging: central artery stiffness, wave reflection, and pressure pulsatility. J Cereb Blood Flow Metab. 2014;34:971–8. doi:10.1038/jcbfm.2014.44.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Webb AJ, Simoni M, Mazzucco S, Kuker W, Schulz U, Rothwell PM. Increased cerebral arterial pulsatility in patients with leukoaraiosis: arterial stiffness enhances transmission of aortic pulsatility. Stroke. 2012;43(10):2631–6. doi:10.1161/STROKEAHA.112.655837.

    Article  PubMed  Google Scholar 

  85. Baumbach GL. Effects of increased pulse pressure on cerebral arterioles. Hypertension. 1996;27(2):159–67.

    Article  CAS  PubMed  Google Scholar 

  86. Baumbach GL, Siems JE, Heistad DD. Effects of local reduction in pressure on distensibility and composition of cerebral arterioles. Circ Res. 1991;68(2):338–51.

    Article  CAS  PubMed  Google Scholar 

  87. Sadekova N, Vallerand D, Guevara E, Lesage F, Girouard H. Carotid calcification in mice: a new model to study the effects of arterial stiffness on the brain. J Am Heart Assoc. 2013;2(3):e000224. doi:10.1161/JAHA.113.000224.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Hajdu MA, Heistad DD, Siems JE, Baumbach GL. Effects of aging on mechanics and composition of cerebral arterioles in rats. Circ Res. 1990;66(6):1747–54.

    Article  CAS  PubMed  Google Scholar 

  89. Faber JE, Zhang H, Lassance-Soares RM, Prabhakar P, Najafi AH, Burnett MS, Epstein SE. Aging causes collateral rarefaction and increased severity of ischemic injury in multiple tissues. Arterioscler Thromb Vasc Biol. 2011;31(8):1748–56. doi:10.1161/ATVBAHA.111.227314. ATVBAHA.111.227314 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Robertson AD, Tessmer CF, Hughson RL. Association between arterial stiffness and cerebrovascular resistance in the elderly. J Hum Hypertens. 2010;24(3):190–6. doi:10.1038/jhh.2009.56.

    Article  CAS  PubMed  Google Scholar 

  91. Cheung N, Islam FM, Jacobs Jr DR, Sharrett AR, Klein R, Polak JF, Cotch MF, Klein BE, Ouyang P, Wong TY. Arterial compliance and retinal vascular caliber in cerebrovascular disease. Ann Neurol. 2007;62(6):618–24. doi:10.1002/ana.21236.

    Article  CAS  PubMed  Google Scholar 

  92. Fonck E, Feigl GG, Fasel J, Sage D, Unser M, Rufenacht DA, Stergiopulos N. Effect of aging on elastin functionality in human cerebral arteries. Stroke. 2009;40(7):2552–6. doi:10.1161/STROKEAHA.108.528091. STROKEAHA.108.528091 [pii].

    Article  CAS  PubMed  Google Scholar 

  93. Brayden JE, Halpern W, Brann LR. Biochemical and mechanical properties of resistance arteries from normotensive and hypertensive rats. Hypertension. 1983;5(1):17–25.

    Article  CAS  PubMed  Google Scholar 

  94. Dorrance AM, Rupp NC, Nogueira EF. Mineralocorticoid receptor activation causes cerebral vessel remodeling and exacerbates the damage caused by cerebral ischemia. Hypertension. 2006;47(3):590–5. doi:10.1161/01.HYP.0000196945.73586.0d. 01.HYP.0000196945.73586.0d [pii].

    Article  CAS  PubMed  Google Scholar 

  95. Izzard AS, Horton S, Heerkens EH, Shaw L, Heagerty AM. Middle cerebral artery structure and distensibility during developing and established phases of hypertension in the spontaneously hypertensive rat. J Hypertens. 2006;24(5):875–80. doi:10.1097/01.hjh.0000222757.54111.06. 00004872-200605000-00015 [pii].

    Article  CAS  PubMed  Google Scholar 

  96. Toda N, Okunishi H, Miyazaki M. Length-passive tension relationships in cerebral and peripheral arteries isolated from spontaneously hypertensive and normotensive rats. Jpn Circ J. 1982;46(10):1088–94.

    Article  CAS  PubMed  Google Scholar 

  97. Baumbach GL, Heistad DD. Remodeling of cerebral arterioles in chronic hypertension. Hypertension. 1989;13(6 Pt 2):968–72.

    Article  CAS  PubMed  Google Scholar 

  98. Baumbach GL, Sigmund CD, Faraci FM. Cerebral arteriolar structure in mice overexpressing human renin and angiotensinogen. Hypertension. 2003;41(1):50–5.

    Article  CAS  PubMed  Google Scholar 

  99. Baumbach GL, Didion SP, Faraci FM. Hypertrophy of cerebral arterioles in mice deficient in expression of the gene for CuZn superoxide dismutase. Stroke. 2006;37(7):1850–5. doi:10.1161/01.STR.0000227236.84546.5a. 01.STR.0000227236.84546.5a [pii].

    Article  CAS  PubMed  Google Scholar 

  100. Baumbach GL, Hajdu MA. Mechanics and composition of cerebral arterioles in renal and spontaneously hypertensive rats. Hypertension. 1993;21(6 Pt 1):816–26.

    Article  CAS  PubMed  Google Scholar 

  101. Baumbach GL, Heistad DD. Mechanics of cerebral arterioles in chronic hypertension. In: Halpern W, editor. Resistance arteries. Ithaca: Perinatology Press; 1988. p. 355–61.

    Google Scholar 

  102. Bugnicourt JM, Da Silveira C, Bengrine A, Godefroy O, Baumbach G, Sevestre H, Bode-Boeger SM, Kielstein JT, Massy ZA, Chillon JM. Chronic renal failure alters endothelial function in cerebral circulation in mice. Am J Physiol Heart Circ Physiol. 2011;301(3):H1143–52. doi:10.1152/ajpheart.01237.2010.

    Article  CAS  PubMed  Google Scholar 

  103. Bugnicourt JM, Leclercq C, Chillon JM, Diouf M, Deramond H, Canaple S, Lamy C, Massy ZA, Godefroy O. Presence of intracranial artery calcification is associated with mortality and vascular events in patients with ischemic stroke after hospital discharge: a cohort study. Stroke. 2011;42(12):3447–53. doi:10.1161/STROKEAHA.111.618652.

    Article  PubMed  Google Scholar 

  104. Bugnicourt JM, Chillon JM, Tribouilloy C, Canaple S, Lamy C, Massy ZA, Godefroy O. Relation between intracranial artery calcifications and aortic atherosclerosis in ischemic stroke patients. J Neurol. 2010;257(8):1338–43. doi:10.1007/s00415-010-5528-1.

    Article  PubMed  Google Scholar 

  105. Baumbach GL, Faraci FM, Heistad DD. Effects of local reduction in pressure on endothelium-dependent responses of cerebral arterioles. Stroke. 1994;25(7):1456–61.

    Article  CAS  PubMed  Google Scholar 

  106. Cheng JJ, Wung BS, Chao YJ, Wang DL. Cyclic strain-induced reactive oxygen species involved in ICAM-1 gene induction in endothelial cells. Hypertension. 1998;31(1):125–30.

    Article  CAS  PubMed  Google Scholar 

  107. Cheng JJ, Wung BS, Chao YJ, Wang DL. Sequential activation of protein kinase C (PKC)-alpha and PKC-epsilon contributes to sustained Raf/ERK1/2 activation in endothelial cells under mechanical strain. J Biol Chem. 2001;276(33):31368–75. doi:10.1074/jbc.M011317200.

    Article  CAS  PubMed  Google Scholar 

  108. Matsushita H, Lee KH, Tsao PS. Cyclic strain induces reactive oxygen species production via an endothelial NAD(P)H oxidase. J Cell Biochem Suppl. 2001;36:99–106.

    Article  PubMed  Google Scholar 

  109. Wang BW, Chang H, Lin S, Kuan P, Shyu KG. Induction of matrix metalloproteinases-14 and −2 by cyclical mechanical stretch is mediated by tumor necrosis factor-alpha in cultured human umbilical vein endothelial cells. Cardiovasc Res. 2003;59(2):460–9.

    Article  CAS  PubMed  Google Scholar 

  110. Bolduc V, Drouin A, Gillis MA, Duquette N, Thorin-Trescases N, Frayne-Robillard I, Des Rosiers C, Tardif JC, Thorin E. Heart rate-associated mechanical stress impairs carotid but not cerebral artery compliance in dyslipidemic atherosclerotic mice. Am J Physiol Heart Circ Physiol. 2011;301(5):H2081–92. doi:10.1152/ajpheart.00706.2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Nigam A, Mitchell GF, Lambert J, Tardif JC. Relation between conduit vessel stiffness (assessed by tonometry) and endothelial function (assessed by flow-mediated dilatation) in patients with and without coronary heart disease. Am J Cardiol. 2003;92(4):395–9. S0002914903006568 [pii].

    Article  PubMed  Google Scholar 

  112. Baumbach GL, Sigmund CD, Faraci FM. Structure of cerebral arterioles in mice deficient in expression of the gene for endothelial nitric oxide synthase. Circ Res. 2004;95(8):822–9. doi:10.1161/01.RES.0000146279.11923.14. 01.RES.0000146279.11923.14 [pii].

    Article  CAS  PubMed  Google Scholar 

  113. Dyrna F, Hanske S, Krueger M, Bechmann I. The blood–brain barrier. J Neuroimmune Pharmacol. 2013;8(4):763–73. doi:10.1007/s11481-013-9473-5.

    Article  PubMed  Google Scholar 

  114. Drouin A, Farhat N, Bolduc V, Thorin-Trescases N, Gillis MA, Villeneuve L, Nguyen A, Thorin E. Up-regulation of thromboxane A(2) impairs cerebrovascular eNOS function in aging atherosclerotic mice. Pflugers Arch. 2011;462(3):371–83. doi:10.1007/s00424-011-0973-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Leblond F, Nguyen A, Bolduc V, Lambert J, Yu C, Duquette N, Thorin E. Postnatal exposure to voluntary exercise but not the antioxidant catechin protects the vasculature after a switch to an atherogenic environment in middle-age mice. Pflugers Arch. 2013;465(2):197–208. doi:10.1007/s00424-012-1206-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Okamoto M, Etani H, Yagita Y, Kinoshita N, Nukada T. Diminished reserve for cerebral vasomotor response to L-arginine in the elderly: evaluation by transcranial Doppler sonography. Gerontology. 2001;47(3):131–5. 52786 [pii].

    Article  CAS  PubMed  Google Scholar 

  117. Nishiyama Y, Ueda M, Katsura K, Otsuka T, Abe A, Nagayama H, Katayama Y. Asymmetric dimethylarginine (ADMA) as a possible risk marker for ischemic stroke. J Neurol Sci. 2010;290(1–2):12–5. doi:10.1016/j.jns.2009.12.020. S0022-510X(09)01023-5 [pii].

    Article  CAS  PubMed  Google Scholar 

  118. Pikula A, Boger RH, Beiser AS, Maas R, DeCarli C, Schwedhelm E, Himali JJ, Schulze F, Au R, Kelly-Hayes M, Kase CS, Vasan RS, Wolf PA, Seshadri S. Association of plasma ADMA levels with MRI markers of vascular brain injury: Framingham offspring study. Stroke. 2009;40(9):2959–64. doi:10.1161/STROKEAHA.109.557116. STROKEAHA.109.557116 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Yoo JH, Lee SC. Elevated levels of plasma homocyst(e)ine and asymmetric dimethylarginine in elderly patients with stroke. Atherosclerosis. 2001;158(2):425–30. S0021-9150(01)00444-0 [pii].

    Article  CAS  PubMed  Google Scholar 

  120. Selley ML. Increased concentrations of homocysteine and asymmetric dimethylarginine and decreased concentrations of nitric oxide in the plasma of patients with Alzheimer’s disease. Neurobiol Aging. 2003;24(7):903–7. S0197458003000071 [pii].

    Article  CAS  PubMed  Google Scholar 

  121. Dayoub H, Rodionov RN, Lynch C, Cooke JP, Arning E, Bottiglieri T, Lentz SR, Faraci FM. Overexpression of dimethylarginine dimethylaminohydrolase inhibits asymmetric dimethylarginine-induced endothelial dysfunction in the cerebral circulation. Stroke. 2008;39(1):180–4. doi:10.1161/STROKEAHA.107.490631. STROKEAHA.107.490631 [pii].

    Article  CAS  PubMed  Google Scholar 

  122. Kielstein JT, Donnerstag F, Gasper S, Menne J, Kielstein A, Martens-Lobenhoffer J, Scalera F, Cooke JP, Fliser D, Bode-Boger SM. ADMA increases arterial stiffness and decreases cerebral blood flow in humans. Stroke. 2006;37(8):2024–9. doi:10.1161/01.STR.0000231640.32543.11. 01.STR.0000231640.32543.11 [pii].

    Article  PubMed  Google Scholar 

  123. Isobe C, Abe T, Terayama Y. Decrease in asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in cerebrospinal fluid during elderly aging and in patients with sporadic form of amyotrophic lateral sclerosis. Neurosignals. 2010;18(1):43–8. doi:10.1159/000312527. 000312527 [pii].

    Article  CAS  PubMed  Google Scholar 

  124. Mayhan WG, Arrick DM, Sharpe GM, Sun H. Age-related alterations in reactivity of cerebral arterioles: role of oxidative stress. Microcirculation. 2008;15(3):225–36. doi:10.1080/10739680701641421. 790020355 [pii].

    Article  CAS  PubMed  Google Scholar 

  125. Modrick ML, Didion SP, Sigmund CD, Faraci FM. Role of oxidative stress and AT1 receptors in cerebral vascular dysfunction with aging. Am J Physiol Heart Circ Physiol. 2009;296(6):H1914–9. doi:10.1152/ajpheart.00300.2009. 00300.2009 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Park L, Anrather J, Girouard H, Zhou P, Iadecola C. Nox2-derived reactive oxygen species mediate neurovascular dysregulation in the aging mouse brain. J Cereb Blood Flow Metab. 2007;27(12):1908–18. doi:10.1038/sj.jcbfm.9600491. 9600491 [pii].

    Article  CAS  PubMed  Google Scholar 

  127. Greenwald SE. Ageing of the conduit arteries. J Pathol. 2007;211(2):157–72. doi:10.1002/path.2101.

    Article  CAS  PubMed  Google Scholar 

  128. Nixon AM, Gunel M, Sumpio BE. The critical role of hemodynamics in the development of cerebral vascular disease. J Neurosurg. 2010;112(6):1240–53. doi:10.3171/2009.10.JNS09759.

    Article  PubMed  Google Scholar 

  129. Marshall RS, Lazar RM. Pumps, aqueducts, and drought management: vascular physiology in vascular cognitive impairment. Stroke. 2011;42(1):221–6. doi:10.1161/STROKEAHA.110.595645.

    Article  PubMed  PubMed Central  Google Scholar 

  130. O’Rourke MF. Arterial aging: pathophysiological principles. Vasc Med. 2007;12(4):329–41. doi:10.1177/1358863X07083392. 12/4/329 [pii].

    Article  PubMed  Google Scholar 

  131. Akima M, Nonaka H, Kagesawa M, Tanaka K. A study on the microvasculature of the cerebral cortex. Fundamental architecture and its senile change in the frontal cortex. Lab Invest. 1986;55(4):482–9.

    CAS  PubMed  Google Scholar 

  132. Aanerud J, Borghammer P, Chakravarty MM, Vang K, Rodell AB, Jonsdottir KY, Moller A, Ashkanian M, Vafaee MS, Iversen P, Johannsen P, Gjedde A. Brain energy metabolism and blood flow differences in healthy aging. J Cereb Blood Flow Metab. 2012;32(7):1177–87. doi:10.1038/jcbfm.2012.18. jcbfm201218 [pii].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Bertsch K, Hagemann D, Hermes M, Walter C, Khan R, Naumann E. Resting cerebral blood flow, attention, and aging. Brain Res. 2009;1267:77–88. doi:10.1016/j.brainres.2009.02.053.

    Article  CAS  PubMed  Google Scholar 

  134. de la Torre JC. Vascular risk factor detection and control may prevent Alzheimer’s disease. Ageing Res Rev. 2010;9(3):218–25. doi:10.1016/j.arr.2010.04.002. S1568-1637(10)00028-0 [pii].

    Article  PubMed  CAS  Google Scholar 

  135. Leenders KL, Perani D, Lammertsma AA, Heather JD, Buckingham P, Healy MJ, Gibbs JM, Wise RJ, Hatazawa J, Herold S, et al. Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age. Brain. 1990;113(Pt 1):27–47.

    Article  PubMed  Google Scholar 

  136. Brown WR, Thore CR. Review: cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol Appl Neurobiol. 2011;37(1):56–74. doi:10.1111/j.1365-2990.2010.01139.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Mosconi L, Mistur R, Switalski R, Tsui WH, Glodzik L, Li Y, Pirraglia E, De Santi S, Reisberg B, Wisniewski T, de Leon MJ. FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2009;36(5):811–22. doi:10.1007/s00259-008-1039-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Yang Y, Rosenberg GA. Blood–brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke. 2011;42(11):3323–8. doi:10.1161/STROKEAHA.110.608257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. de la Torre JC. Cerebral hypoperfusion, capillary degeneration, and development of Alzheimer disease. Alzheimer Dis Assoc Disord. 2000;14 Suppl 1:S72–81.

    Article  PubMed  Google Scholar 

  140. de la Torre JC. How do heart disease and stroke become risk factors for Alzheimer’s disease? Neurol Res. 2006;28(6):637–44. doi:10.1179/016164106X130362.

    Article  PubMed  Google Scholar 

  141. de la Torre JC. A turning point for Alzheimer’s disease? Biofactors. 2012;38(2):78–83. doi:10.1002/biof.200.

    Article  PubMed  CAS  Google Scholar 

  142. Iadecola C, Park L, Capone C. Threats to the mind: aging, amyloid, and hypertension. Stroke. 2009;40(3 Suppl):S40–4. doi:10.1161/STROKEAHA.108.533638. STROKEAHA.108.533638 [pii].

    Article  PubMed  PubMed Central  Google Scholar 

  143. Marchal G, Rioux P, Petit-Taboue MC, Sette G, Travere JM, Le Poec C, Courtheoux P, Derlon JM, Baron JC. Regional cerebral oxygen consumption, blood flow, and blood volume in healthy human aging. Arch Neurol. 1992;49(10):1013–20.

    Article  CAS  PubMed  Google Scholar 

  144. Pantano P, Baron JC, Lebrun-Grandie P, Duquesnoy N, Bousser MG, Comar D. Regional cerebral blood flow and oxygen consumption in human aging. Stroke. 1984;15(4):635–41.

    Article  CAS  PubMed  Google Scholar 

  145. Braak H, Rub U, Schultz C, Del Tredici K. Vulnerability of cortical neurons to Alzheimer’s and Parkinson’s diseases. J Alzheimers Dis. 2006;9(3 Suppl):35–44.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Funding: This research on cerebrovascular aging is supported by the Canadian Institutes of Health Research (MOP 89733), the Montreal Heart Institute Foundation, and the Heart and Stroke Foundation of Quebec.

Conflict of Interest: none.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eric Thorin Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Chillon, JM., Thorin, E. (2016). Arterial Stiffness and the Brain. In: Girouard, H. (eds) Hypertension and the Brain as an End-Organ Target. Springer, Cham. https://doi.org/10.1007/978-3-319-25616-0_7

Download citation

Publish with us

Policies and ethics