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Pathophysiology of Brain Damage in Hypertension: Small Vessel Disease

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Hypertension and Brain Damage

Part of the book series: Updates in Hypertension and Cardiovascular Protection ((UHCP))

Abstract

Structural abnormalities of microvessels are common alterations associated with chronic hypertension. Changes in the microvascular structure of the cerebral circulation, both in terms of an increased media-lumen ratio of cerebral small resistance arteries or the wall-to-lumen ratio of retinal arterioles, as well as capillary rarefaction, may have important pathophysiological and clinical consequences. Cerebral small vessel disease is associated with an increased risk of death, ischemic stroke and cognitive decline. Changes in large artery stiffness induced by hypertension may be related to microvascular alterations and contribute to cerebrovascular events, including cerebral microbleeds. Although the brain may play a crucial role in the onset of essential hypertension, it is also a main target of the detrimental effects of high blood pressure, and changes in small artery structuring are crucial mechanisms involved in the development of the brain damage induced by hypertension.

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References

  1. Mulvany MJ, Aalkjaer C (1990) Structure and function of small arteries. Physiol Rev 70:921–971

    CAS  PubMed  Google Scholar 

  2. Schiffrin EL (2004) Remodeling of resistance arteries in essential hypertension and effects of antihypertensive treatment. Am J Hypertens 17(12 Pt 1):1192–1200

    Article  CAS  PubMed  Google Scholar 

  3. Izzard AS, Rizzoni D, Agabiti-Rosei E, Heagerty AM (2005) Small artery structure and hypertension: adaptive changes and target organ damage. J Hypertens 23:247–250

    Article  CAS  PubMed  Google Scholar 

  4. Aalkjaer C, Haegerty AM, Petersen KK, Swales JD, Mulvany MJ (1987) Evidence for increased media thickness, increased neural amine uptake, and depressed excitation-contraction coupling in isolated resistance vessels from essential hypertensives. Circ Res 61(2):181–186

    Article  CAS  PubMed  Google Scholar 

  5. Aalkjaer C, Eiskjaer H, Mulvany MJ, Jespersen B, Kjaer T, Sorensen SS, Pedersen EB (1989) Abnormal structure and function of isolated subcutaneous resistance vessels from essential hypertensive patients despite antihypertensive treatment. J Hypertens 7:305–310

    CAS  PubMed  Google Scholar 

  6. Heagerty AM, Aalkjaaer C, Bund SJ, Korsgaard N, Mulvany MJ (1993) Small artery structure in hypertension. Dual process of remodeling and growth. Hypertension 21:391–397

    Article  CAS  PubMed  Google Scholar 

  7. Rizzoni D, Porteri E, Castellano M, Bettoni G, Muiesan ML, Muiesan P, Giulini SM, Agabiti Rosei E (1996) Vascular hypertrophy and remodeling in secondary hypertension. Hypertension 28:785–790

    Article  CAS  PubMed  Google Scholar 

  8. Rizzoni D, Porteri E, Guelfi D, Muiesan ML, Valentini U, Cimino A, Girelli A, Rodella L, Bianchi R, Sleiman I, Agabiti Rosei E (2001) Structural alterations in subcutaneous small arteries of normotensive and hypertensive patients with non-insulin dependent diabetes mellitus. Circulation 103:1238–1244

    Article  CAS  PubMed  Google Scholar 

  9. Rizzoni D, Porteri E, Guelfi D, Piccoli A, Castellano M, Pasini G, Muiesan ML, Mulvany MJ, Agabiti Rosei E (2000) Cellular hypertrophy in subcutaneous small arteries of patients with renovascular hypertension. Hypertension 35:931–935

    Article  CAS  PubMed  Google Scholar 

  10. Rizzoni D, Palombo C, Porteri E, Muiesan ML, Kozàkovà M, La Canna G, Nardi M, Guelfi D, Salvetti M, Morizzo C, Vittone F, Agabiti Rosei E (2003) Relationships between coronary vasodilator capacity and small artery remodeling in hypertensive patients. J Hypertens 21:625–632

    Article  CAS  PubMed  Google Scholar 

  11. Rizzoni D, Porteri E, Boari GEM, De Ciuceis C, Sleiman I, Muiesan ML, Castellano M, Miclini M, Agabiti-Rosei E (2003) Prognostic significance of small artery structure in hypertension. Circulation 108:2230–2235

    Article  PubMed  Google Scholar 

  12. De Ciuceis C, Porteri E, Rizzoni D, Rizzardi N, Paiardi S, Boari GEM, Miclini M, Zani F, Muiesan ML, Donato F, Salvetti M, Castellano M, Tiberio GA, Giulini SM, Agabiti Rosei E (2007) Structural alterations of subcutaneous small arteries may predict major cardiovascular events in hypertensive patients. Am J Hypertens 20:846–852

    Article  PubMed  Google Scholar 

  13. Mathiassen ON, Buus NH, Sihm I, Thybo NK, Morn B, Schroeder AP, Thygesen K, Aalkjaer C, Lederballe O, Mulvany MJ, Christensen KL (2007) Small artery structure is an independent predictor of cardiovascular events in essential hypertension. J Hypertens 25:1021–1026

    Article  CAS  PubMed  Google Scholar 

  14. Rizzoni D, Porteri E, Platto C, Rizzardi N, De Ciuceis C, Boari GEM, Muiesan ML, Salvetti M, Zani F, Miclini M, Paiardi S, Castellano M, Agabiti Rosei E (2007) Morning rise of blood pressure and subcutaneous small resistance artery structure. J Hypertens 25:1698–1703

    Article  CAS  PubMed  Google Scholar 

  15. Buus NH, Mathiassen ON, Fenger-Grøn M, Præstholm MN, Sihm I, Thybo NK, Schroeder AP, Thygesen K, Aalkjær C, Pedersen OL, Mulvany MJ, Christensen KL (2013) Small artery structure during antihypertensive therapy is an independent predictor of cardiovascular events in essential hypertension. J Hypertens 31:791–797

    Article  CAS  PubMed  Google Scholar 

  16. Mulvany MJ (2007) Small artery structure: time to take note? (editorial commentary). Am J Hypertens 20:853–854

    Article  PubMed  Google Scholar 

  17. Agabiti Rosei E, Rizzoni D (2007) Chapter 47: The effects of hypertension on the structure of human resistance arteries. In: Lip GYH, Hall JE (eds) Comprehensive hypertension. Mosby Elsevier, Philadelphia, pp 579–590

    Chapter  Google Scholar 

  18. Agabiti-Rosei E, Heagerty AM, Rizzoni D (2009) Effects of antihypertensive treatment on small artery remodelling. J Hypertens 27(6):1107–1114

    Article  CAS  PubMed  Google Scholar 

  19. Mathiassen ON, Buus NH, Larsen ML, Mulvany MJ, Christensen KL (2007) Small artery structure adapts to vasodilatation rather than to blood pressure during antihypertensive treatment. J Hypertens 25:1027–1034

    Article  CAS  PubMed  Google Scholar 

  20. Savoia C, Touyz RM, Endemann DH, Pu Q, Ko EA, De Ciuceis C, Schiffrin EL (2006) Angiotensin receptor blocker added to previous antihypertensive agents on arteries of diabetic hypertensive patients. Hypertension 48:271–277

    Article  CAS  PubMed  Google Scholar 

  21. Rizzoni D, Porteri E, De Ciuceis C, Sleiman I, Rodella L, Rezzani R, Paiardi S, Bianchi R, Ruggeri G, Boari GEM, Muiesan ML, Salvetti M, Zani F, Miclini M, Agabiti Rosei E (2005) Effects of treatment with candesartan or enalapril on subcutaneous small resistance artery structure in hypertensive patients with NIDDM. Hypertension 45(Part 2):659–665

    Article  CAS  PubMed  Google Scholar 

  22. Park JB, Integan HD, Schiffrin EL (2000) Reduction of resistance artery stiffness by treatment with the AT(1)-receptor antagonist losartan in essential hypertension. J Renin Angiotensin Aldosterone Syst 1:40–45

    Article  CAS  PubMed  Google Scholar 

  23. Savoia C, Touyz RM, Amiri F, Schiffrin EL (2008) Selective mineralocorticoid receptor blocker eplerenone reduces resistance artery stiffness in hypertensive patients. Hypertension 51:432–439

    Article  CAS  PubMed  Google Scholar 

  24. Smith RD, Yokoyama H, Averill DB, Schiffrin EL, Ferrario CM (2008) Reversal of vascular hypertrophy in hypertensive patients through blockade of angiotensin II receptors. J Am Soc Hypertens 2:165–172

    Article  PubMed  Google Scholar 

  25. Dickinson J, Paton JFR (2012) Cerebrovascular hypertension. Book Guild Publishing, Sussex, pp 3–257

    Google Scholar 

  26. Faraci FM, Baumbach GL, Heistad DD (1989) Myogenic mechanisms in the cerebral circulation. J Hypertens Suppl 7:S61–S64

    CAS  PubMed  Google Scholar 

  27. Baumbach GL, Heistad DD (1985) Regional, segmental, and temporal heterogeneity of cerebral vascular autoregulation. Ann Biomed Eng 13(3–4):303–310

    Article  CAS  PubMed  Google Scholar 

  28. Faraci FM, Baumbach GL, Heistad DD (1990) Cerebral circulation: humoral regulation and effects of chronic hypertension. J Am Soc Nephrol 1(1):53–57

    CAS  PubMed  Google Scholar 

  29. Jordan JD, Powers WJ (2012) Cerebral autoregulation and acute ischemic stroke. Am J Hypertens 25:946–950

    Article  PubMed  Google Scholar 

  30. Rizzoni D, Ciuceis C, Porteri E, Paiardi S, Boari GEM, Mortini P, Cornali C, Cenzato M, Rodella LF, Borsani E, Rizzardi N, Platto C, Rezzani R, Agabiti Rosei E (2009) Altered structure of small cerebral arteries in patients with essential hypertension. J Hypertens 27(4):838–845

    Article  CAS  PubMed  Google Scholar 

  31. Antonios TF, Singer DR, Markandu ND, Mortimer PS, MacGregor GA (1999) Structural skin capillary rarefaction in essential hypertension. Hypertension 33:998–1001

    Article  CAS  PubMed  Google Scholar 

  32. De Ciuceis C, Cornali C, Porteri E, Mardighian D, Pinardi C, Fontanella MM, Rodella LF, Rezzani R, Rizzoni D, Boari GE, Agabiti Rosei E, Gasparotti R (2014) Cerebral small-resistance artery structure and cerebral blood flow in normotensive subjects and hypertensive patients. Neuroradiology 56:1103–1111

    Article  PubMed  Google Scholar 

  33. Ringelstein EB, Knecht S (2006) Cerebral small vessel diseases: manifestations in young women. Curr Opin Neurol 19:55–62

    Article  PubMed  Google Scholar 

  34. Baumgartner RW, Sidler C, Mosso M, Georgiadis D (2003) Ischemic lacunar stroke in patients with and without potential mechanism other than small-artery disease. Stroke 34:653–659

    Article  PubMed  Google Scholar 

  35. Dickinson CJ (2001) Why are strokes related to hypertension? Classic studies and hypotheses revisited. J Hypertens 19:1515–1521

    Article  CAS  PubMed  Google Scholar 

  36. Munzenmaier DH, Greene AS (2006) Chronic angiotensin II AT1 receptor blockade increases cerebral cortical microvessel density. Am J Physiol Heart Circ Physiol 290(2):H512–H516

    Article  CAS  PubMed  Google Scholar 

  37. Greene AS, Tonellato PJ, Lui J, Lombard JH, Cowley AW Jr (1989) Microvascular rarefaction and tissue vascular resistance in hypertension. Am J Physiol 256:H126–H131

    CAS  PubMed  Google Scholar 

  38. Izzard AS, Horton S, Heerkens EH, Shaw L, Heagerty AM (2006) Middle cerebral artery structure and distensibility during developing and established phases of hypertension in the spontaneously hypertensive rat. J Hypertens 24:875–880

    Article  CAS  PubMed  Google Scholar 

  39. Hajdu MA, Baumbach GL (1994) Mechanics of large and small cerebral arteries in chronic hypertension. Am J Physiol 266(3 Pt 2):H1027–H1033

    CAS  PubMed  Google Scholar 

  40. Baumbach GL, Hajdu MA (1993) Mechanics and composition of cerebral arterioles in renal and spontaneously hypertensive rats. Hypertension 21(6 Pt 1):816–826

    Article  CAS  PubMed  Google Scholar 

  41. Izzard AS, Graham D, Burnham MP, Heerkens EH, Dominiczak AF, Heagerty AM (2003) Myogenic and structural properties of cerebral arteries from the stroke-prone spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol 285:H1489–H1494

    Article  CAS  PubMed  Google Scholar 

  42. Hajdu MA, Heistad DD, Siems JE, Baumbach GL (1990) Effects of aging on mechanics and composition of cerebral arterioles in rats. Circ Res 66:1747–1754

    Article  CAS  PubMed  Google Scholar 

  43. Thybo NK, Mulvany MJ, Jastrup B, Nielsen H, Aalkjaer C (1996) Some pharmacological and elastic characteristics of isolated subcutaneous small arteries from patients with essential hypertension. J Hypertens 14:993–998

    Article  CAS  PubMed  Google Scholar 

  44. Intengan HD, Deng LY, Li JS, Schiffrin EL (1999) Mechanics and composition of human subcutaneous resistance arteries in essential hypertension. Hypertension 33(1 Pt 2):569–574

    Article  CAS  PubMed  Google Scholar 

  45. Hashimoto J, Aikawa T, Imai Y (2008) Large artery stiffening as a link between cerebral lacunar infarction and renal albuminuria. Am J Hypertens 21(12):1304–1309

    Article  CAS  PubMed  Google Scholar 

  46. Brisset M, Boutouyrie P, Pico F, Zhu Y, Zureik M, Schilling S, Dufouil C, Mazoyer B, Laurent S, Tzourio C, Debette S (2013) Large-vessel correlates of cerebral small-vessel disease. Neurology 80:662–669

    Article  PubMed  PubMed Central  Google Scholar 

  47. Wåhlin A, Ambarki K, Birgander R, Malm J, Eklund A (2014) Intracranial pulsatility is associated with regional brain volume in elderly individuals. Neurobiol Aging 35:365–372

    Article  PubMed  Google Scholar 

  48. O'Rourke MF, Safar ME (2005) Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension 46:200–204

    Article  PubMed  Google Scholar 

  49. Waldstein SR, Rice SC, Thayer JF, Najjar SS, Scuteri A, Zonderman AB (2008) Pulse pressure and pulse wave velocity are related to cognitive decline in the Baltimore Longitudinal Study of Aging. Hypertension 51:99–104

    Article  CAS  PubMed  Google Scholar 

  50. Mitchell GF, van Buchem MA, Sigurdsson S, Gotal JD, Jonsdottir MK, Kjartansson Ó, Garcia M, Aspelund T, Harris TB, Gudnason V, Launer LJ (2011) Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility–Reykjavik study. Brain 134(Pt 11):3398–3407

    Article  PubMed  PubMed Central  Google Scholar 

  51. O'Rourke MF, Hashimoto J (2007) Mechanical factors in arterial aging: a clinical perspective. J Am Coll Cardiol 50(1):1–13

    Article  PubMed  Google Scholar 

  52. Webb AJ, Simoni M, Mazzucco S, Kuker W, Schulz U, Rothwell PM (2012) Increased cerebral arterial pulsatility in patients with leukoaraiosis: arterial stiffness enhances transmission of aortic pulsatility. Stroke 43:2631–2636

    Article  PubMed  Google Scholar 

  53. Wong TY, Mitchell P (2004) Hypertensive retinopathy. N Engl J Med 351:2310–2317

    Article  CAS  PubMed  Google Scholar 

  54. Harazny JM, Ritt M, Baleanu D, Ott C, Heckmann J, Schlaich MP, Michelson G, Schmieder RE (2007) Increased wall:lumen ratio of retinal arterioles in male patients with a history of a cerebrovascular event. Hypertension 50(4):623–829

    Article  CAS  PubMed  Google Scholar 

  55. Ritt M, Harazny JM, Ott C, Schlaich MP, Schneider MP, Michelson G, Schmieder RE (2008) Analysis of retinal arteriolar structure in never-treated patients with essential hypertension. J Hypertens 26(7):1427–1434

    Article  CAS  PubMed  Google Scholar 

  56. Ritt M, Harazny JM, Ott C, Schneider MP, Schlaich MP, Michelson G, Schmieder RE (2009) Wall-to-lumen ratio of retinal arterioles is related with urinary albumin excretion and altered vascular reactivity to infusion of the nitric oxide synthase inhibitor N-monomethyl-L-arginine. J Hypertens 27:2201–2218

    Article  CAS  PubMed  Google Scholar 

  57. Rizzoni D, Porteri E, Duse S, De Ciuceis C, Agabiti Rosei C, La Boria E, Semeraro F, Costagliola C, Sebastiani A, Danzi P, Tiberio GA, Giulini SM, Docchio F, Sansoni G, Sarkar A, Agabiti Rosei E (2012) Relationship between media to lumen ratio of subcutaneous small arteries and wall to lumen ratio of retinal arterioles evaluated non-invasively by scanning laser-Doppler flowmetry. J Hypertens 30:1169–1175

    Article  CAS  PubMed  Google Scholar 

  58. Ott C, Raff U, Harazny JM, Michelson G, Schmieder RE (2013) Central pulse pressure is an independent determinant of vascular remodeling in the retinal circulation. Hypertension 61:1340–1345

    Article  CAS  PubMed  Google Scholar 

  59. Salvetti M, Agabiti Rosei C, Paini A, Aggiusti C, Cancarini A, Duse S, Semeraro F, Rizzoni D, Agabiti Rosei E, Muiesan ML (2014) Relationship of wall-to-lumen ratio of retinal arterioles with clinic and 24-hour blood pressure. Hypertension 63:1110–1115

    Article  CAS  PubMed  Google Scholar 

  60. Laurent S, Briet M, Boutouyrie P (2009) Large and small artery cross-talk and recent morbidity-mortality trials in hypertension. Hypertension 54:388–392

    Article  CAS  PubMed  Google Scholar 

  61. Muiesan ML, Salvetti M, Rizzoni D, Paini A, Agabiti-Rosei C, Aggiusti C, Bertacchini F, Stassaldi D, Gavazzi A, Porteri E, De Ciuceis C, Agabiti-Rosei E (2013) Pulsatile hemodynamics and microcirculation: evidence for a close relationship in hypertensive patients. Hypertension 61:130–136

    Article  CAS  PubMed  Google Scholar 

  62. Conijn MM, Kloppenborg RP, Algra A, Mali WP, Kappelle LJ, Vincken KL, van der Graaf Y, Geerlings MI, SMART Study Group (2011) Cerebral small vessel disease and risk of death, ischemic stroke, and cardiac complications in patients with atherosclerotic disease: the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study. Stroke 42:3105–3109

    Article  CAS  PubMed  Google Scholar 

  63. Ding JD, Mitchell GF, Bots ML, Sigurdsson S, Harris TB, Garcia M, Eiriksdottir G, van Buchem MA, Gudnason V, Launer LJ (2015) Carotid artery stiffness and risk of incident cerebral microbleeds in older people. The age, gene/environment susceptibility (AGES)- Reykjavik study. Arterioscler Thromb Vasc Biol 35:1889–1895

    Article  CAS  PubMed  Google Scholar 

  64. Heagerty AM (2007) Predicting hypertension complications from small artery structure. J Hypertens 25:939–940

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

    Enrico Agabiti-Rosei & Damiano Rizzoni

  2. Clinica Medica, Department of Medical and Surgical Sciences, University of Brescia, c/o 2a Medicina, Spedali Civili., Brescia, 25100, Italy

    Enrico Agabiti-Rosei

  3. Division of Medicine, Istituto Clinico Città di Brescia, Brescia, Italy

    Damiano Rizzoni

  4. Department of Internal Medicine, Centro Hospitalar do Alto Ave. University of Minho, Guimarães, Portugal

    Pedro Cunha

Authors
  1. Enrico Agabiti-Rosei
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  2. Damiano Rizzoni
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  3. Pedro Cunha
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Correspondence to Enrico Agabiti-Rosei .

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  1. Hypertension & Vascular Risk Unit, Hospital Clínic, Barcelona, Spain

    Antonio Coca

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Agabiti-Rosei, E., Rizzoni, D., Cunha, P. (2016). Pathophysiology of Brain Damage in Hypertension: Small Vessel Disease. In: Coca, A. (eds) Hypertension and Brain Damage. Updates in Hypertension and Cardiovascular Protection. Springer, Cham. https://doi.org/10.1007/978-3-319-32074-8_5

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  • DOI: https://doi.org/10.1007/978-3-319-32074-8_5

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