Skip to main content
SpringerLink
Log in

The Effects of Hypertension on Cerebral Artery Structure and Function, and Cerebral Blood Flow

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

Abstract

Careful regulation of cerebral blood flow is required to maintain proper brain function. The cerebral arteries are particularly sensitive to the effects of hypertension, which alters the arteries in a manner that impairs the brains ability to tightly regulate perfusion. This chapter focuses the effects of hypertension on cerebral artery structure and function, with emphasis on myogenic reactivity and endothelium-dependent dilation. Hypertension causes a reduction in the lumen diameter of cerebral arteries and this is often associated with an increase in the wall-to-lumen ratio. Several circulating factors have been implicated in mediating this inward artery remodeling; these include aldosterone, angiotensin II, proinflammatory cytokines, and reactive oxygen species. Endothelium-dependent dilation in response to nitric oxide and epoxyeicosatrienoic acids is impaired in hypertension; this leads to increases in myogenic tone and impaired dilation. Dysfunction of ion channels, including calcium-activated potassium channels and transient receptor potential (TRP) V4 channels, has also been associated with impaired endothelial function in hypertensive models. Understanding the mechanisms responsible for the hypertension-associated vascular dysfunction is important because hypertension is associated with an increased risk of dementia and stroke and with increased ischemic injury in the event of a stroke.

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

Access this chapter

Log in via an institution
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

Abbreviations

20-HETE:

20-Hydroxyeicosatetraenoic acid

2K2C:

2-Kidney 2-clip

ACE:

Angiotensin-converting enzyme

BBB:

Blood brain barrier

BKCa :

Ca2+-activated potassium channels

CaCC:

Ca2+-activated Cl− channels

DOCA:

Deoxycorticosterone acetate

EDHF:

Endothelial-dependent hyperpolarizing factor

EETs:

Epoxyeicosatrienoic acids

eNOS:

Endothelial NO synthase

ICl.Ca :

Ca2+-activated Cl− current

ICl.vol :

Volume-regulated Cl− channel

IKCa :

Intermediate-conductance Ca2+-activated K+ channels

l-NAME:

N-Nitro-l-arginine methyl ester

MMP:

Matrix metalloproteinase

NO:

Nitric oxide

PPARγ:

Peroxisome proliferator-activated receptor γ

RAAS:

Renin angiotensin aldosterone system

SHR:

Spontaneously hypertensive rats

SHRSP:

Stroke-prone spontaneously hypertensive rats

SKCa :

Small-conductance Ca2+-activated K+

TRP:

Transient receptor potential

References

  1. Vander AJ, Sherman JH, Luciano DS. Human physiology: the mechanisms of body function. 5th ed. New York: McGraw-Hill; 1990.

    Google Scholar 

  2. Madl C, Holzer M. Brain function after resuscitation from cardiac arrest. Curr Opin Crit Care. 2004;10(3):213–7.

    Article  PubMed  Google Scholar 

  3. de la Torre JC. Cardiovascular risk factors promote brain hypoperfusion leading to cognitive decline and dementia. Cardiovasc Psychiatry Neurol. 2012;2012:367516.

    PubMed  PubMed Central  Google Scholar 

  4. Faraci FM. Protecting against vascular disease in brain. Am J Physiol Heart Circ Physiol. 2011;300(5):H1566–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lewington S, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903–13.

    Article  PubMed  Google Scholar 

  6. Kengne AP, et al. Systolic blood pressure, diabetes and the risk of cardiovascular diseases in the Asia-Pacific region. J Hypertens. 2007;25(6):1205–13.

    Article  CAS  PubMed  Google Scholar 

  7. Go AS, et al. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation. 2013;127(1):e6–245.

    Article  PubMed  Google Scholar 

  8. Sierra C, et al. Hypertension and mild cognitive impairment. Curr Hypertens Rep. 2012;14(6):548–55.

    Article  CAS  PubMed  Google Scholar 

  9. Kelley BJ, Petersen RC. Alzheimer’s disease and mild cognitive impairment. Neurol Clin. 2007;25(3):577–609. v.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Skoog I, Gustafson D. Update on hypertension and Alzheimer’s disease. Neurol Res. 2006;28(6):605–11.

    Article  PubMed  Google Scholar 

  11. Cipolla MJ. The cerebral circulation. San Rafael: Morgan & Claypool Life Sciences; 2009.

    Google Scholar 

  12. Dirnagl U. Pathobiology of injury after stroke: the neurovascular unit and beyond. Ann N Y Acad Sci. 2012;1268:21–5.

    Article  PubMed  Google Scholar 

  13. 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 

  14. Abbott NJ, et al. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37(1):13–25.

    Article  CAS  PubMed  Google Scholar 

  15. Berman SA, Hayman LA, Hinck VC. Correlation of CT cerebral vascular territories with function: 3. Middle cerebral artery. Am J Roentgenol. 1984;142(5):1035–40.

    Article  CAS  Google Scholar 

  16. Hayman LA, Berman SA, Hinck VC. Correlation of CT cerebral vascular territories with function: II. Posterior cerebral artery. Am J Roentgenol. 1981;137(1):13–9.

    Article  CAS  Google Scholar 

  17. Berman SA, Hayman LA, Hinck VC. Correlation of CT cerebral vascular territories with function: I. Anterior cerebral artery. Am J Roentgenol. 1980;135(2):253–7.

    Article  CAS  Google Scholar 

  18. Coyle P, Jokelainen PT. Dorsal cerebral arterial collaterals of the rat. Anat Rec. 1982;203(3):397–404.

    Article  CAS  PubMed  Google Scholar 

  19. Schaffer CB, et al. Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion. PLoS Biol. 2006;4(2):e22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Coyle P, Heistad DD. Blood flow through cerebral collateral vessels in hypertensive and normotensive rats. Hypertension. 1986;8(6 Pt 2):II67–71.

    CAS  PubMed  Google Scholar 

  21. Coyle P, Jokelainen PT. Differential outcome to middle cerebral artery occlusion in spontaneously hypertensive stroke-prone rats (SHRSP) and Wistar Kyoto (WKY) rats. Stroke. 1983;14(4):605–11.

    Article  CAS  PubMed  Google Scholar 

  22. Bohlen HG. The microcirculation in hypertension. J Hypertens Suppl. 1989;7(4):S117–24.

    CAS  PubMed  Google Scholar 

  23. Hamel E. Perivascular nerves and the regulation of cerebrovascular tone. J Appl Physiol. 2006;100(3):1059–64.

    Article  PubMed  Google Scholar 

  24. Iadecola C, Davisson RL. Hypertension and cerebrovascular dysfunction. Cell Metab. 2008;7(6):476–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Shih AY, et al. The smallest stroke: occlusion of one penetrating vessel leads to infarction and a cognitive deficit. Nat Neurosci. 2013;16(1):55–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Nishimura N, et al. Penetrating arterioles are a bottleneck in the perfusion of neocortex. Proc Natl Acad Sci U S A. 2007;104(1):365–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gobel U, Theilen H, Kuschinsky W. Congruence of total and perfused capillary network in rat brains. Circ Res. 1990;66(2):271–81.

    Article  CAS  PubMed  Google Scholar 

  28. Sa-Pereira I, Brites D, Brito MA. Neurovascular unit: a focus on pericytes. Mol Neurobiol. 2012;45(2):327–47.

    Article  CAS  PubMed  Google Scholar 

  29. Dalkara T, Gursoy-Ozdemir Y, Yemisci M. Brain microvascular pericytes in health and disease. Acta Neuropathol. 2011;122(1):1–9.

    Article  PubMed  Google Scholar 

  30. Shepro D, Morel NM. Pericyte physiology. Faseb J. 1993;7(11):1031–8.

    CAS  PubMed  Google Scholar 

  31. Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev. 2005;57(2):173–85.

    Article  CAS  PubMed  Google Scholar 

  32. Koehler RC, Gebremedhin D, Harder DR. Role of astrocytes in cerebrovascular regulation. J Appl Physiol. 2006;100(1):307–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Stanimirovic DB, Friedman A. Pathophysiology of the neurovascular unit: disease cause or consequence? J Cereb Blood Flow Metab. 2012;32(7):1207–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cohen Z, Molinatti G, Hamel E. Astroglial and vascular interactions of noradrenaline terminals in the rat cerebral cortex. J Cereb Blood Flow Metab. 1997;17(8):894–904.

    Article  CAS  PubMed  Google Scholar 

  35. Hogestatt ED, Andersson KE. On the postjunctional alpha-adrenoreceptors in rat cerebral and mesenteric arteries. J Auton Pharmacol. 1984;4(3):161–73.

    Article  CAS  PubMed  Google Scholar 

  36. Duckworth JW, et al. Aminergic histofluorescence and contractile responses to transmural electrical field stimulation and norepinephrine of human middle cerebral arteries obtained promptly after death. Circ Res. 1989;65(2):316–24.

    Article  CAS  PubMed  Google Scholar 

  37. Lincoln J. Innervation of cerebral arteries by nerves containing 5-hydroxytryptamine and noradrenaline. Pharmacol Ther. 1995;68(3):473–501.

    Article  CAS  PubMed  Google Scholar 

  38. Sokolova IA, et al. Rarefication of the arterioles and capillary network in the brain of rats with different forms of hypertension. Microvasc Res. 1985;30(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  39. Suzuki K, et al. Pathologic evidence of microvascular rarefaction in the brain of renal hypertensive rats. J Stroke Cerebrovasc Dis. 2003;12(1):8–16.

    Article  PubMed  Google Scholar 

  40. Paiardi S, et al. Immunohistochemical evaluation of microvascular rarefaction in hypertensive humans and in spontaneously hypertensive rats. Clin Hemorheol Microcirc. 2009;42(4):259–68.

    CAS  PubMed  Google Scholar 

  41. Joutel A, et al. Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease. J Clin Invest. 2010;120(2):433–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Coyle P, Heistad DD. Blood flow through cerebral collateral vessels one month after middle cerebral artery occlusion. Stroke. 1987;18(2):407–11.

    Article  CAS  PubMed  Google Scholar 

  43. Harper SL, Bohlen HG. Microvascular adaptation in the cerebral cortex of adult spontaneously hypertensive rats. Hypertension. 1984;6(3):408–19.

    Article  CAS  PubMed  Google Scholar 

  44. Werber AH, et al. No rarefaction of cerebral arterioles in hypertensive rats. Can J Physiol Pharmacol. 1990;68(4):476–9.

    Article  CAS  PubMed  Google Scholar 

  45. Noon JP, et al. Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure. J Clin Invest. 1997;99(8):1873–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Serne EH, et al. Impaired skin capillary recruitment in essential hypertension is caused by both functional and structural capillary rarefaction. Hypertension. 2001;38(2):238–42.

    Article  CAS  PubMed  Google Scholar 

  47. Serne EH, et al. Capillary recruitment is impaired in essential hypertension and relates to insulin’s metabolic and vascular actions. Cardiovasc Res. 2001;49(1):161–8.

    Article  CAS  PubMed  Google Scholar 

  48. Nazzaro P, et al. Effect of clustering of metabolic syndrome factors on capillary and cerebrovascular impairment. Eur J Intern Med. 2013;24(2):183–8.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  50. Mulvany MJ, et al. Vascular remodeling. Hypertension. 1996;28(3):505–6.

    CAS  PubMed  Google Scholar 

  51. Heagerty AM, et al. Small artery structure in hypertension. Dual processes of remodeling and growth. Hypertension. 1993;21(4):391–7.

    Article  CAS  PubMed  Google Scholar 

  52. Folkow B, et al. Importance of adaptive changes in vascular design for establishment of primary hypertension, studied in man and in spontaneously hypertensive rats. Circ Res. 1973;32 Suppl 1:2–16.

    PubMed  Google Scholar 

  53. Baumbach GL, Chillon JM. Effects of angiotensin-converting enzyme inhibitors on cerebral vascular structure in chronic hypertension. J Hypertens Suppl. 2000;18(1):S7–11.

    Article  CAS  PubMed  Google Scholar 

  54. Heistad DD, et al. Impaired dilatation of cerebral arterioles in chronic hypertension. Blood Vessels. 1990;27(2–5):258–62.

    CAS  PubMed  Google Scholar 

  55. Mulvany MJ. Small artery remodelling in hypertension. Basic Clin Pharmacol Toxicol. 2012;110(1):49–55.

    Article  CAS  PubMed  Google Scholar 

  56. Pires PW, et al. The effects of hypertension on the cerebral circulation. Am J Physiol Heart Circ Physiol. 2013;304(12):H1598–614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hayashi K, Naiki T. Adaptation and remodeling of vascular wall; biomechanical response to hypertension. J Mech Behav Biomed Mater. 2009;2(1):3–19.

    Article  PubMed  Google Scholar 

  58. Baumbach GL, Heistad DD. Cerebral circulation in chronic arterial hypertension. Hypertension. 1988;12(2):89–95.

    Article  CAS  PubMed  Google Scholar 

  59. Laurent S, Boutouyrie P, Lacolley P. Structural and genetic bases of arterial stiffness. Hypertension. 2005;45(6):1050–5.

    Article  CAS  PubMed  Google Scholar 

  60. Mulvany MJ. Small artery remodeling and significance in the development of hypertension. News Physiol Sci. 2002;17:105–9.

    PubMed  Google Scholar 

  61. Izzard AS, et al. Small artery structure and hypertension: adaptive changes and target organ damage. J Hypertens. 2005;23(2):247–50.

    Article  CAS  PubMed  Google Scholar 

  62. De Ciuceis C, et al. Structural alterations of subcutaneous small-resistance arteries may predict major cardiovascular events in patients with hypertension. Am J Hypertens. 2007;20(8):846–52.

    Article  PubMed  Google Scholar 

  63. Dorrance AM, et al. A high-potassium diet reduces infarct size and improves vascular structure in hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2007;292(1):R415–22.

    Article  CAS  PubMed  Google Scholar 

  64. Rigsby CS, Pollock DM, Dorrance AM. Spironolactone improves structure and increases tone in the cerebral vasculature of male spontaneously hypertensive stroke-prone rats. Microvasc Res. 2007;73(3):198–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Deutsch C, et al. Diet-induced obesity causes cerebral vessel remodeling and increases the damage caused by ischemic stroke. Microvasc Res. 2009;78(1):100–6.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Osmond JM, et al. Obesity increases blood pressure, cerebral vascular remodeling, and severity of stroke in the Zucker rat. Hypertension. 2009;53(2):381–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. 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.

    Article  CAS  PubMed  Google Scholar 

  68. Osmond JM, Dorrance AM. 11beta-hydroxysteroid dehydrogenase type II inhibition causes cerebrovascular remodeling and increases infarct size after cerebral ischemia. Endocrinology. 2009;150(2):713–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Moreau P, et al. Structure and function of the rat basilar artery during chronic nitric oxide synthase inhibition. Stroke. 1995;26(10):1922–8. discussion 1928-9.

    Article  CAS  PubMed  Google Scholar 

  70. 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 

  71. Baumbach GL, et al. Mechanics of cerebral arterioles in hypertensive rats. Circ Res. 1988;62(1):56–64.

    Article  CAS  PubMed  Google Scholar 

  72. Davidson AO, et al. Blood pressure in genetically hypertensive rats influence of the Y chromosome. Hypertension. 1995;26(3):452–9.

    Article  CAS  PubMed  Google Scholar 

  73. Pires PW, et al. Doxycycline, a matrix metalloprotease inhibitor, reduces vascular remodeling and damage after cerebral ischemia in stroke-prone spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 2011;301(1):H87–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Chan SL, Sweet JG, Cipolla MJ. Treatment for cerebral small vessel disease: effect of relaxin on the function and structure of cerebral parenchymal arterioles during hypertension. FASEB J. 2013;27(10):3917–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Osmond JM, Mintz JD, Stepp DW. Preventing increased blood pressure in the obese Zucker rat improves severity of stroke. Am J Physiol Heart Circ Physiol. 2010;299(1):H55–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Arribas SM, et al. Functional reduction and associated cellular rearrangement in SHRSP rat basilar arteries are affected by salt load and calcium antagonist treatment. J Cereb Blood Flow Metab. 1999;19(5):517–27.

    Article  CAS  PubMed  Google Scholar 

  77. Arribas SM, et al. Confocal microscopic characterization of a lesion in a cerebral vessel of the stroke-prone spontaneously hypertensive rat. Stroke. 1996;27(6):1118–22. discussion 1122-3.

    Article  CAS  PubMed  Google Scholar 

  78. Arribas SM, et al. Cellular changes induced by chronic nitric oxide inhibition in intact rat basilar arteries revealed by confocal microscopy. J Hypertens. 1997;15(12 Pt 2):1685–93.

    Article  CAS  PubMed  Google Scholar 

  79. Hajdu MA, Heistad DD, Baumbach GL. Effects of antihypertensive therapy on mechanics of cerebral arterioles in rats. Hypertension. 1991;17(3):308–16.

    Article  CAS  PubMed  Google Scholar 

  80. Clozel JP, Kuhn H, Hefti F. Effects of cilazapril on the cerebral circulation in spontaneously hypertensive rats. Hypertension. 1989;14(6):645–51.

    Article  CAS  PubMed  Google Scholar 

  81. Dupuis F, et al. Comparative effects of the angiotensin II receptor blocker, telmisartan, and the angiotensin-converting enzyme inhibitor, ramipril, on cerebrovascular structure in spontaneously hypertensive rats. J Hypertens. 2005;23(5):1061–6.

    Article  CAS  PubMed  Google Scholar 

  82. Chillon JM, Baumbach GL. Effects of an angiotensin-converting enzyme inhibitor and a beta-blocker on cerebral arterioles in rats. Hypertension. 1999;33(3):856–61.

    Article  PubMed  Google Scholar 

  83. Yamakawa H, et al. Normalization of endothelial and inducible nitric oxide synthase expression in brain microvessels of spontaneously hypertensive rats by angiotensin II AT1 receptor inhibition. J Cereb Blood Flow Metab. 2003;23(3):371–80.

    Article  CAS  PubMed  Google Scholar 

  84. Kumai Y, et al. Protective effects of angiotensin II type 1 receptor blocker on cerebral circulation independent of blood pressure. Exp Neurol. 2008;210(2):441–8.

    Article  CAS  PubMed  Google Scholar 

  85. Blumenfeld JD, et al. Beta-adrenergic receptor blockade as a therapeutic approach for suppressing the renin-angiotensin-aldosterone system in normotensive and hypertensive subjects. Am J Hypertens. 1999;12(5):451–9.

    Article  CAS  PubMed  Google Scholar 

  86. Dupuis F, et al. Effects of suboptimal doses of the AT1 receptor blocker, telmisartan, with the angiotensin-converting enzyme inhibitor, ramipril, on cerebral arterioles in spontaneously hypertensive rat. J Hypertens. 2010;28(7):1566–73.

    Article  CAS  PubMed  Google Scholar 

  87. Dupuis F, et al. Captopril improves cerebrovascular structure and function in old hypertensive rats. Br J Pharmacol. 2005;144(3):349–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Foulquier S, et al. Differential effects of short-term treatment with two AT1 receptor blockers on diameter of pial arterioles in SHR. PLoS One. 2012;7(9):e42469.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Foulquier S, Lartaud I, Dupuis F. Impact of Short-Term Treatment with Telmisartan on Cerebral Arterial Remodeling in SHR. PLoS One. 2014;9(10):e110766.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Maeda K, et al. Larger anastomoses in angiotensinogen-knockout mice attenuate early metabolic disturbances after middle cerebral artery occlusion. J Cereb Blood Flow Metab. 1999;19(10):1092–8.

    Article  CAS  PubMed  Google Scholar 

  91. Rigsby CS, et al. Effects of spironolactone on cerebral vessel structure in rats with sustained hypertension. Am J Hypertens. 2011;24(6):708–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Chrissobolis S, et al. Chronic aldosterone administration causes Nox2-mediated increases in reactive oxygen species production and endothelial dysfunction in the cerebral circulation. J Hypertens. 2014;32(9):1815–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Inaba S, et al. Temporary treatment with AT1 receptor blocker, valsartan, from early stage of hypertension prevented vascular remodeling. Am J Hypertens. 2011;24(5):550–6.

    Article  CAS  PubMed  Google Scholar 

  94. Harrap SB, et al. Brief angiotensin converting enzyme inhibitor treatment in young spontaneously hypertensive rats reduces blood pressure long-term. Hypertension. 1990;16(6):603–14.

    Article  CAS  PubMed  Google Scholar 

  95. Kost Jr CK, Li P, Jackson EK. Blood pressure after captopril withdrawal from spontaneously hypertensive rats. Hypertension. 1995;25(1):82–7.

    Article  CAS  PubMed  Google Scholar 

  96. McClain JL, Dorrance AM. Temporary mineralocorticoid receptor antagonism during the development of hypertension improves cerebral artery dilation. Exp Biol Med (Maywood). 2014;239(5):619–27.

    Article  CAS  Google Scholar 

  97. Touyz RM, Tabet F, Schiffrin EL. Redox-dependent signalling by angiotensin II and vascular remodelling in hypertension. Clin Exp Pharmacol Physiol. 2003;30(11):860–6.

    Article  CAS  PubMed  Google Scholar 

  98. Queisser N, Fazeli G, Schupp N. Superoxide anion and hydrogen peroxide-induced signaling and damage in angiotensin II and aldosterone action. Biol Chem. 2010;391(11):1265–79.

    Article  CAS  PubMed  Google Scholar 

  99. Park JB, et al. Chronic treatment with a superoxide dismutase mimetic prevents vascular remodeling and progression of hypertension in salt-loaded stroke-prone spontaneously hypertensive rats. Am J Hypertens. 2002;15(1 Pt 1):78–84.

    Article  CAS  PubMed  Google Scholar 

  100. Bonacasa B, et al. 2-Methoxyestradiol attenuates hypertension and coronary vascular remodeling in spontaneously hypertensive rats. Maturitas. 2008;61(4):310–6.

    Article  CAS  PubMed  Google Scholar 

  101. Pires PW, et al. Tempol, a superoxide dismutase mimetic, prevents cerebral vessel remodeling in hypertensive rats. Microvasc Res. 2010;80(3):445–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res. 2002;90(3):251–62.

    CAS  PubMed  Google Scholar 

  103. Patel VB, et al. Angiotensin-converting enzyme 2 is a critical determinant of angiotensin II-induced loss of vascular smooth muscle cells and adverse vascular remodeling. Hypertension. 2014;64(1):157–64.

    Article  CAS  PubMed  Google Scholar 

  104. Switzer JA, et al. Minocycline prevents IL-6 increase after acute ischemic stroke. Transl Stroke Res. 2012;3(3):363–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Switzer JA, et al. Matrix metalloproteinase-9 in an exploratory trial of intravenous minocycline for acute ischemic stroke. Stroke. 2011;42(9):2633–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Cipolla MJ, et al. PPAR{gamma} activation prevents hypertensive remodeling of cerebral arteries and improves vascular function in female rats. Stroke. 2010;41(6):1266–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Ledingham JM, Laverty R. Effects of glitazones on blood pressure and vascular structure in mesenteric resistance arteries and basilar artery from genetically hypertensive rats. Clin Exp Pharmacol Physiol. 2005;32(11):919–25.

    Article  CAS  PubMed  Google Scholar 

  108. Ledingham JM, Laverty R. Effect of simvastatin given alone and in combination with valsartan or enalapril on blood pressure and the structure of mesenteric resistance arteries and the basilar artery in the genetically hypertensive rat model. Clin Exp Pharmacol Physiol. 2005;32(1–2):76–85.

    Article  PubMed  Google Scholar 

  109. Liu YJ, et al. Simvastatin ameliorates rat cerebrovascular remodeling during hypertension via inhibition of volume-regulated chloride channel. Hypertension. 2010;56(3):445–52.

    Article  CAS  PubMed  Google Scholar 

  110. Strange K. Cellular volume homeostasis. Adv Physiol Educ. 2004;28(1–4):155–9.

    Article  PubMed  Google Scholar 

  111. Cai BX, et al. Ginsenoside-Rd, a new voltage-independent Ca2+ entry blocker, reverses basilar hypertrophic remodeling in stroke-prone renovascular hypertensive rats. Eur J Pharmacol. 2009;606(1-3):142–9.

    Article  CAS  PubMed  Google Scholar 

  112. Inoue R, et al. Transient receptor potential channels in cardiovascular function and disease. Circ Res. 2006;99(2):119–31.

    Article  CAS  PubMed  Google Scholar 

  113. Xie MJ, et al. Functional alterations in cerebrovascular K(+) and Ca(2+) channels are comparable between simulated microgravity rat and SHR. Am J Physiol Heart Circ Physiol. 2005;289(3):H1265–76.

    Article  CAS  PubMed  Google Scholar 

  114. Guan YY, Wang GL, Zhou JG. The ClC-3 Cl− channel in cell volume regulation, proliferation and apoptosis in vascular smooth muscle cells. Trends Pharmacol Sci. 2006;27(6):290–6.

    Article  CAS  PubMed  Google Scholar 

  115. Zhou JG, et al. Regulation of intracellular Cl− concentration through volume-regulated ClC-3 chloride channels in A10 vascular smooth muscle cells. J Biol Chem. 2005;280(8):7301–8.

    Article  CAS  PubMed  Google Scholar 

  116. Nelson MT, et al. Chloride channel blockers inhibit myogenic tone in rat cerebral arteries. J Physiol. 1997;502(Pt 2):259–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Shi XL, et al. Alteration of volume-regulated chloride movement in rat cerebrovascular smooth muscle cells during hypertension. Hypertension. 2007;49(6):1371–7.

    Article  CAS  PubMed  Google Scholar 

  118. Zheng LY, et al. Deficiency of volume-regulated ClC-3 chloride channel attenuates cerebrovascular remodelling in DOCA-salt hypertension. Cardiovasc Res. 2013;100(1):134–42.

    Article  CAS  PubMed  Google Scholar 

  119. Zeng JW, et al. Integrin beta3 mediates cerebrovascular remodelling through Src/ClC-3 volume-regulated Cl(−) channel signalling pathway. Br J Pharmacol. 2014;171(13):3158–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Duan DD. The ClC-3 chloride channels in cardiovascular disease. Acta Pharmacol Sin. 2011;32(6):675–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Cribbs LL. T-type Ca2+ channels in vascular smooth muscle: multiple functions. Cell Calcium. 2006;40(2):221–30.

    Article  CAS  PubMed  Google Scholar 

  122. Potier M, et al. Evidence for STIM1- and Orai1-dependent store-operated calcium influx through ICRAC in vascular smooth muscle cells: role in proliferation and migration. Faseb J. 2009;23(8):2425–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Wang M, et al. Downregulation of TMEM16A calcium-activated chloride channel contributes to cerebrovascular remodeling during hypertension by promoting basilar smooth muscle cell proliferation. Circulation. 2012;125(5):697–707.

    Article  CAS  PubMed  Google Scholar 

  124. Schiffrin EL. Immune mechanisms in hypertension and vascular injury. Clin Sci (Lond). 2014;126(4):267–74.

    Article  CAS  Google Scholar 

  125. Crowley SD. The cooperative roles of inflammation and oxidative stress in the pathogenesis of hypertension. Antioxid Redox Signal. 2014;20(1):102–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Schiffrin EL. The immune system: role in hypertension. Can J Cardiol. 2013;29(5):543–8.

    Article  PubMed  Google Scholar 

  127. Kassan M, et al. CD4+CD25+Foxp3 regulatory T cells and vascular dysfunction in hypertension. J Hypertens. 2013;31(10):1939–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Schiffrin EL. Immune modulation of resistance artery remodelling. Basic Clin Pharmacol Toxicol. 2012;110(1):70–2.

    Article  CAS  PubMed  Google Scholar 

  129. Knorr M, Munzel T, Wenzel P. Interplay of NK cells and monocytes in vascular inflammation and myocardial infarction. Front Physiol. 2014;5:295.

    Article  PubMed  PubMed Central  Google Scholar 

  130. Shen JZ, Young MJ. Corticosteroids, heart failure, and hypertension: a role for immune cells? Endocrinology. 2012;153(12):5692–700.

    Article  CAS  PubMed  Google Scholar 

  131. Luft FC, Dechend R, Muller DN. Immune mechanisms in angiotensin II-induced target-organ damage. Ann Med. 2012;44 Suppl 1:S49–54.

    Article  CAS  PubMed  Google Scholar 

  132. Pires PW, et al. Improvement in middle cerebral artery structure and endothelial function in stroke-prone spontaneously hypertensive rats after macrophage depletion. Microcirculation. 2013;20:650–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Elmarakby AA, et al. Tumor necrosis factor alpha blockade increases renal Cyp2c23 expression and slows the progression of renal damage in salt-sensitive hypertension. Hypertension. 2006;47(3):557–62.

    Article  CAS  PubMed  Google Scholar 

  134. Elmarakby AA, et al. TNF-alpha inhibition reduces renal injury in DOCA-salt hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2008;294(1):R76–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Pires PW, et al. Tumor necrosis factor-alpha inhibition attenuates middle cerebral artery remodeling but increases cerebral ischemic damage in hypertensive rats. Am J Physiol Heart Circ Physiol. 2014;307(5):H658–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Jennings JR, et al. Reduced cerebral blood flow response and compensation among patients with untreated hypertension. Neurology. 2005;64(8):1358–65.

    Article  CAS  PubMed  Google Scholar 

  137. Kety SS, Hafkenschiel JH, et al. The blood flow, vascular resistance, and oxygen consumption of the brain in essential hypertension. J Clin Invest. 1948;27(4):511–4.

    Article  CAS  PubMed Central  Google Scholar 

  138. Beason-Held LL, et al. Longitudinal changes in cerebral blood flow in the older hypertensive brain. Stroke. 2007;38(6):1766–73.

    Article  PubMed  Google Scholar 

  139. Muller M, et al. Hypertension and longitudinal changes in cerebral blood flow: the SMART-MR study. Ann Neurol. 2012;71:825–33.

    Article  PubMed  Google Scholar 

  140. Go AS, et al. Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation. 2014;129(3):e28–292.

    Article  PubMed  Google Scholar 

  141. Tomonaga M, et al. Clinicopathologic study of progressive subcortical vascular encephalopathy (Binswanger type) in the elderly. J Am Geriatr Soc. 1982;30(8):524–9.

    Article  CAS  PubMed  Google Scholar 

  142. Furuta A, et al. Medullary arteries in aging and dementia. Stroke. 1991;22(4):442–6.

    Article  CAS  PubMed  Google Scholar 

  143. Hajdu MA, et al. Effects of aging on mechanics and composition of cerebral arterioles in rats. Circ Res. 1990;66(6):1747–54.

    Article  CAS  PubMed  Google Scholar 

  144. Moreau P, d’Uscio LV, Luscher TF. Structure and reactivity of small arteries in aging. Cardiovasc Res. 1998;37(1):247–53.

    Article  CAS  PubMed  Google Scholar 

  145. Fonck E, et al. Effect of aging on elastin functionality in human cerebral arteries. Stroke. 2009;40(7):2552–6.

    Article  CAS  PubMed  Google Scholar 

  146. Li ML, et al. Atherosclerosis of middle cerebral artery: evaluation with high-resolution MR imaging at 3T. Atherosclerosis. 2009;204(2):447–52.

    Article  CAS  PubMed  Google Scholar 

  147. Dunn KM, Nelson MT. Neurovascular signaling in the brain and the pathological consequences of hypertension. Am J Physiol Heart Circ Physiol. 2014;306(1):H1–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Bloch S, Obari D, Girouard H. Angiotensin and neurovascular coupling: beyond hypertension. Microcirculation. 2015;22:159–67.

    CAS  PubMed  Google Scholar 

  149. Kazama K, et al. Angiotensin II attenuates functional hyperemia in the mouse somatosensory cortex. Am J Physiol Heart Circ Physiol. 2003;285(5):H1890–9.

    Article  CAS  PubMed  Google Scholar 

  150. Capone C, et al. The cerebrovascular dysfunction induced by slow pressor doses of angiotensin II precedes the development of hypertension. Am J Physiol Heart Circ Physiol. 2011;300(1):H397–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Kazama K, et al. Angiotensin II impairs neurovascular coupling in neocortex through NADPH oxidase-derived radicals. Circ Res. 2004;95(10):1019–26.

    Article  CAS  PubMed  Google Scholar 

  152. Calcinaghi N, et al. Multimodal imaging in rats reveals impaired neurovascular coupling in sustained hypertension. Stroke. 2013;44(7):1957–64.

    Article  PubMed  Google Scholar 

  153. Paulson OB, Strandgaard S, Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev. 1990;2(2):161–92.

    CAS  PubMed  Google Scholar 

  154. Osol G, et al. Myogenic tone, reactivity, and forced dilatation: a three-phase model of in vitro arterial myogenic behavior. Am J Physiol Heart Circ Physiol. 2002;283(6):H2260–7.

    Article  CAS  PubMed  Google Scholar 

  155. Talman WT, Nitschke Dragon D. Neuronal nitric oxide mediates cerebral vasodilatation during acute hypertension. Brain Res. 2007;1139:126–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Duchemin S, et al. The complex contribution of NOS interneurons in the physiology of cerebrovascular regulation. Front Neural Circuits. 2012;6:51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  157. Jones SC, et al. Cortical NOS inhibition raises the lower limit of cerebral blood flow-arterial pressure autoregulation. Am J Physiol. 1999;276(4 Pt 2):H1253–62.

    CAS  PubMed  Google Scholar 

  158. Hamner JW, et al. Sympathetic control of the cerebral vasculature in humans. Stroke. 2010;41(1):102–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Hamner JW, et al. Cholinergic control of the cerebral vasculature in humans. J Physiol. 2012;590(Pt 24):6343–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  161. Bayliss WM. On the local reactions of the arterial wall to changes of internal pressure. J Physiol. 1902;28(3):220–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Faraci FM, Baumbach GL, Heistad DD. Myogenic mechanisms in the cerebral circulation. J Hypertens Suppl. 1989;7(4):S61–4. discussion S65.

    CAS  PubMed  Google Scholar 

  163. Geary GG, Krause DN, Duckles SP. Estrogen reduces mouse cerebral artery tone through endothelial NOS- and cyclooxygenase-dependent mechanisms. Am J Physiol Heart Circ Physiol. 2000;279(2):H511–9.

    CAS  PubMed  Google Scholar 

  164. Cipolla MJ, Porter JM, Osol G. High glucose concentrations dilate cerebral arteries and diminish myogenic tone through an endothelial mechanism. Stroke. 1997;28(2):405–10. discussion 410-1.

    Article  CAS  PubMed  Google Scholar 

  165. Faraci FM, Brian Jr JE. Nitric oxide and the cerebral circulation. Stroke. 1994;25(3):692–703.

    Article  CAS  PubMed  Google Scholar 

  166. Malomvolgyi B, et al. Relaxation by prostacyclin (PGI2) and 7-oxo-PGI2 of isolated cerebral, coronary and mesenteric arteries. Acta Physiol Acad Sci Hung. 1982;60(4):251–6.

    CAS  PubMed  Google Scholar 

  167. Gonzales RJ, Krause DN, Duckles SP. Testosterone suppresses endothelium-dependent dilation of rat middle cerebral arteries. Am J Physiol Heart Circ Physiol. 2004;286(2):H552–60.

    Article  CAS  PubMed  Google Scholar 

  168. Dunn KM, et al. Elevated production of 20-HETE in the cerebral vasculature contributes to severity of ischemic stroke and oxidative stress in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 2008;295(6):H2455–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Gebremedhin D, et al. Production of 20-HETE and its role in autoregulation of cerebral blood flow. Circ Res. 2000;87(1):60–5.

    Article  CAS  PubMed  Google Scholar 

  170. Osol G, Halpern W. Myogenic properties of cerebral blood vessels from normotensive and hypertensive rats. Am J Physiol. 1985;249(5 Pt 2):H914–21.

    CAS  PubMed  Google Scholar 

  171. Jarajapu YP, Knot HJ. Relative contribution of Rho kinase and protein kinase C to myogenic tone in rat cerebral arteries in hypertension. Am J Physiol Heart Circ Physiol. 2005;289(5):H1917–22.

    Article  CAS  PubMed  Google Scholar 

  172. Ibrahim J, et al. Sex-specific differences in cerebral arterial myogenic tone in hypertensive and normotensive rats. Am J Physiol Heart Circ Physiol. 2006;290(3):H1081–9.

    Article  CAS  PubMed  Google Scholar 

  173. Izzard AS, et al. Myogenic and structural properties of cerebral arteries from the stroke-prone spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol. 2003;285(4):H1489–94.

    Article  CAS  PubMed  Google Scholar 

  174. Smeda JS, VanVliet BN, King SR. Stroke-prone spontaneously hypertensive rats lose their ability to auto-regulate cerebral blood flow prior to stroke. J Hypertens. 1999;17(12 Pt 1):1697–705.

    Article  CAS  PubMed  Google Scholar 

  175. Ishizuka T, et al. Involvement of thromboxane A2 receptor in the cerebrovascular damage of salt-loaded, stroke-prone rats. J Hypertens. 2007;25(4):861–70.

    Article  CAS  PubMed  Google Scholar 

  176. Griffin KA, et al. Differential salt-sensitivity in the pathogenesis of renal damage in SHR and stroke prone SHR. Am J Hypertens. 2001;14(4 Pt 1):311–20.

    Article  CAS  PubMed  Google Scholar 

  177. Toth P, et al. Age-related autoregulatory dysfunction and cerebromicrovascular injury in mice with angiotensin II-induced hypertension. J Cereb Blood Flow Metab. 2013;33(11):1732–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Toth P, et al. Role of 20-HETE, TRPC channels, and BKCa in dysregulation of pressure-induced Ca2+ signaling and myogenic constriction of cerebral arteries in aged hypertensive mice. Am J Physiol Heart Circ Physiol. 2013;305(12):H1698–708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Welsh DG, et al. Transient receptor potential channels regulate myogenic tone of resistance arteries. Circ Res. 2002;90(3):248–50.

    Article  CAS  PubMed  Google Scholar 

  180. Earley S, Waldron BJ, Brayden JE. Critical role for transient receptor potential channel TRPM4 in myogenic constriction of cerebral arteries. Circ Res. 2004;95(9):922–9.

    Article  CAS  PubMed  Google Scholar 

  181. Gonzales AL, et al. A PLCgamma1-dependent, force-sensitive signaling network in the myogenic constriction of cerebral arteries. Sci Signal. 2014;7(327):ra49.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  182. Li Y, et al. TRPM4 channels couple purinergic receptor mechanoactivation and myogenic tone development in cerebral parenchymal arterioles. J Cereb Blood Flow Metab. 2014;34(10):1706–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  183. Barry DI. Cerebral blood flow in hypertension. J Cardiovasc Pharmacol. 1985;7 Suppl 2:S94–8.

    Article  PubMed  Google Scholar 

  184. Barry DI, et al. Effects of captopril on cerebral blood flow in normotensive and hypertensive rats. Am J Med. 1984;76(5B):79–85.

    Article  CAS  PubMed  Google Scholar 

  185. Vorstrup S, et al. Chronic antihypertensive treatment in the rat reverses hypertension-induced changes in cerebral blood flow autoregulation. Stroke. 1984;15(2):312–8.

    Article  CAS  PubMed  Google Scholar 

  186. Coyle P. Dorsal cerebral collaterals of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY). Anat Rec. 1987;218(1):40–4.

    Article  CAS  PubMed  Google Scholar 

  187. Huang Z, et al. Enlarged infarcts in endothelial nitric oxide synthase knockout mice are attenuated by nitro-L-arginine. J Cereb Blood Flow Metab. 1996;16(5):981–7.

    Article  CAS  PubMed  Google Scholar 

  188. Oyama N, et al. Cilostazol, not aspirin, reduces ischemic brain injury via endothelial protection in spontaneously hypertensive rats. Stroke. 2011;42(9):2571–7.

    Article  CAS  PubMed  Google Scholar 

  189. Omote Y, et al. Clinical and pathological improvement in stroke-prone spontaneous hypertensive rats related to the pleiotropic effect of cilostazol. Stroke. 2012;43:1639–46.

    Article  CAS  PubMed  Google Scholar 

  190. Shinohara Y, et al. Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial. Lancet Neurol. 2010;9(10):959–68.

    Article  CAS  PubMed  Google Scholar 

  191. Touyz RM, Briones AM. Reactive oxygen species and vascular biology: implications in human hypertension. Hypertens Res. 2011;34(1):5–14.

    Article  CAS  PubMed  Google Scholar 

  192. Paravicini TM, Sobey CG. Cerebral vascular effects of reactive oxygen species: recent evidence for a role of NADPH-oxidase. Clin Exp Pharmacol Physiol. 2003;30(11):855–9.

    Article  CAS  PubMed  Google Scholar 

  193. Miller AA, et al. NADPH oxidase activity and function are profoundly greater in cerebral versus systemic arteries. Circ Res. 2005;97(10):1055–62.

    Article  CAS  PubMed  Google Scholar 

  194. Sobey CG, Heistad DD, Faraci FM. Mechanisms of bradykinin-induced cerebral vasodilatation in rats. Evidence that reactive oxygen species activate K+ channels. Stroke. 1997;28(11):2290–4. discussion 2295.

    Article  CAS  PubMed  Google Scholar 

  195. Chaplin NL, Amberg GC. Hydrogen peroxide mediates oxidant-dependent stimulation of arterial smooth muscle L-type calcium channels. Am J Physiol Cell Physiol. 2012;302(9):C1382–93.

    Article  CAS  PubMed  Google Scholar 

  196. Paravicini TM, Drummond GR, Sobey CG. Reactive oxygen species in the cerebral circulation: physiological roles and therapeutic implications for hypertension and stroke. Drugs. 2004;64(19):2143–57.

    Article  CAS  PubMed  Google Scholar 

  197. Bryan Jr RM, et al. Endothelium-derived hyperpolarizing factor: a cousin to nitric oxide and prostacyclin. Anesthesiology. 2005;102(6):1261–77.

    Article  CAS  PubMed  Google Scholar 

  198. Stankevicius E, et al. Opening of small and intermediate calcium-activated potassium channels induces relaxation mainly mediated by nitric-oxide release in large arteries and endothelium-derived hyperpolarizing factor in small arteries from rat. J Pharmacol Exp Ther. 2011;339(3):842–50.

    Article  CAS  PubMed  Google Scholar 

  199. Si H, et al. Impaired endothelium-derived hyperpolarizing factor-mediated dilations and increased blood pressure in mice deficient of the intermediate-conductance Ca2 + -activated K+ channel. Circ Res. 2006;99(5):537–44.

    Article  CAS  PubMed  Google Scholar 

  200. Marrelli SP, Eckmann MS, Hunte MS. Role of endothelial intermediate conductance KCa channels in cerebral EDHF-mediated dilations. Am J Physiol Heart Circ Physiol. 2003;285(4):H1590–9.

    Article  CAS  PubMed  Google Scholar 

  201. Giachini FR, et al. Upregulation of intermediate calcium-activated potassium channels counterbalance the impaired endothelium-dependent vasodilation in stroke-prone spontaneously hypertensive rats. Transl Res. 2009;154(4):183–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Earley S, Brayden JE. Transient receptor potential channels and vascular function. Clin Sci (Lond). 2010;119(1):19–36.

    Article  CAS  Google Scholar 

  203. Venkatachalam K, Montell C. TRP channels. Annu Rev Biochem. 2007;76:387–417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Reading SA, et al. TRPC3 mediates pyrimidine receptor-induced depolarization of cerebral arteries. Am J Physiol Heart Circ Physiol. 2005;288(5):H2055–61.

    Article  CAS  PubMed  Google Scholar 

  205. Noorani MM, Noel RC, Marrelli SP. Upregulated TRPC3 and downregulated TRPC1 channel expression during hypertension is associated with increased vascular contractility in rat. Front Physiol. 2011;2:42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Earley S, et al. TRPV4 forms a novel Ca2+ signaling complex with ryanodine receptors and BKCa channels. Circ Res. 2005;97(12):1270–9.

    Article  CAS  PubMed  Google Scholar 

  207. Earley S. Endothelium-dependent cerebral artery dilation mediated by transient receptor potential and Ca2+-activated K+ channels. J Cardiovasc Pharmacol. 2011;57(2):148–53.

    Article  CAS  PubMed  Google Scholar 

  208. Dorrance AM, et al. An epoxide hydrolase inhibitor, 12-(3-adamantan-1-yl-ureido)dodecanoic acid (AUDA), reduces ischemic cerebral infarct size in stroke-prone spontaneously hypertensive rats. J Cardiovasc Pharmacol. 2005;46(6):842–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Simpkins AN, et al. Soluble epoxide inhibition is protective against cerebral ischemia via vascular and neural protection. Am J Pathol. 2009;174(6):2086–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Cheng H, Lederer WJ. Calcium sparks. Physiol Rev. 2008;88(4):1491–545.

    Article  CAS  PubMed  Google Scholar 

  211. Sonkusare SK, et al. Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science. 2012;336(6081):597–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Xi Q, Cheranov SY, Jaggar JH. Mitochondria-derived reactive oxygen species dilate cerebral arteries by activating Ca2+ sparks. Circ Res. 2005;97(4):354–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Earley S, et al. TRPV4-dependent dilation of peripheral resistance arteries influences arterial pressure. Am J Physiol Heart Circ Physiol. 2009;297(3):H1096–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Harder DR, et al. Functional hyperemia in the brain: hypothesis for astrocyte-derived vasodilator metabolites. Stroke. 1998;29(1):229–34.

    Article  CAS  PubMed  Google Scholar 

  215. Iliff JJ, et al. Epoxyeicosanoids as mediators of neurogenic vasodilation in cerebral vessels. Am J Physiol Heart Circ Physiol. 2009;296(5):H1352–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Girouard H, Iadecola C. Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol. 2006;100(1):328–35.

    Article  CAS  PubMed  Google Scholar 

  217. Dirnagl U, et al. Coupling of cerebral blood flow to neuronal activation: role of adenosine and nitric oxide. Am J Physiol. 1994;267(1 Pt 2):H296–301.

    CAS  PubMed  Google Scholar 

  218. Lindauer U, et al. Nitric oxide: a modulator, but not a mediator, of neurovascular coupling in rat somatosensory cortex. Am J Physiol. 1999;277(2 Pt 2):H799–811.

    CAS  PubMed  Google Scholar 

  219. Niwa K, et al. Cyclooxygenase-2 contributes to functional hyperemia in whisker-barrel cortex. J Neurosci. 2000;20(2):763–70.

    CAS  PubMed  Google Scholar 

  220. Roman RJ. P-450 metabolites of arachidonic acid in the control of cardiovascular function. Physiol Rev. 2002;82(1):131–85.

    Article  CAS  PubMed  Google Scholar 

  221. Zeldin DC. Epoxygenase pathways of arachidonic acid metabolism. J Biol Chem. 2001;276(39):36059–62.

    Article  CAS  PubMed  Google Scholar 

  222. Vriens J, et al. Modulation of the Ca2 permeable cation channel TRPV4 by cytochrome P450 epoxygenases in vascular endothelium. Circ Res. 2005;97(9):908–15.

    Article  CAS  PubMed  Google Scholar 

  223. Imig JD, et al. Soluble epoxide hydrolase inhibition lowers arterial blood pressure in angiotensin II hypertension. Hypertension. 2002;39(2 Pt 2):690–4.

    Article  CAS  PubMed  Google Scholar 

  224. Sporkova A, et al. Role of cytochrome P-450 metabolites in the regulation of renal function and blood pressure in 2-kidney 1-clip hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2011;300(6):R1468–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Manhiani M, et al. Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension. Am J Physiol Renal Physiol. 2009;297(3):F740–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  226. Liu X, et al. Interaction of nitric oxide, 20-HETE, and EETs during functional hyperemia in whisker barrel cortex. Am J Physiol Heart Circ Physiol. 2008;295(2):H619–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Cipolla MJ, et al. Threshold duration of ischemia for myogenic tone in middle cerebral arteries: effect on vascular smooth muscle actin. Stroke. 2001;32(7):1658–64.

    Article  CAS  PubMed  Google Scholar 

  228. Mayhan WG, et al. Responses of cerebral arteries after ischemia and reperfusion in cats. Am J Physiol. 1988;255(4 Pt 2):H879–84.

    CAS  PubMed  Google Scholar 

  229. Rosenblum WI, Wormley B. Selective depression of endothelium-dependent dilations during cerebral ischemia. Stroke. 1995;26(10):1877–81. discussion 1882.

    Article  CAS  PubMed  Google Scholar 

  230. Cipolla MJ, et al. Reperfusion decreases myogenic reactivity and alters middle cerebral artery function after focal cerebral ischemia in rats. Stroke. 1997;28(1):176–80.

    Article  CAS  PubMed  Google Scholar 

  231. Cipolla MJ, Curry AB. Middle cerebral artery function after stroke: the threshold duration of reperfusion for myogenic activity. Stroke. 2002;33(8):2094–9.

    Article  PubMed  Google Scholar 

  232. Jimenez-Altayo F, et al. Transient middle cerebral artery occlusion causes different structural, mechanical, and myogenic alterations in normotensive and hypertensive rats. Am J Physiol Heart Circ Physiol. 2007;293(1):H628–35.

    Article  CAS  PubMed  Google Scholar 

  233. Coucha M, Li W, Ergul A. The effect of endothelin receptor A antagonism on basilar artery endothelium-dependent relaxation after ischemic stroke. Life Sci. 2012;91:676–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Cipolla MJ, et al. Postischemic reperfusion causes smooth muscle calcium sensitization and vasoconstriction of parenchymal arterioles. Stroke. 2014;45(8):2425–30.

    Article  PubMed  PubMed Central  Google Scholar 

  235. Martinez-Revelles S, et al. Endothelial dysfunction in rat mesenteric resistance artery after transient middle cerebral artery occlusion. J Pharmacol Exp Ther. 2008;325(2):363–9.

    Article  CAS  PubMed  Google Scholar 

  236. Kimura S, et al. Pathogenesis of vascular dementia in stroke-prone spontaneously hypertensive rats. Toxicology. 2000;153(1–3):167–78.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Nevada at Reno School of Medicine, 1664 North Virginia Street, Manville Health Sciences, Reno, NV, 89557, USA

    Paulo W. Pires

  2. Department of Pharmacology and Toxicology, Michigan State University, B340 Life Sciences Building, 1355 Bogue Street, East Lansing, MI, 48824, USA

    Anne M. Dorrance

Authors
  1. Paulo W. Pires
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne M. Dorrance
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne M. Dorrance .

Editor information

Editors and Affiliations

  1. Faculty of Medicine, Université de Montréal, Montréal, Canada

    Hélène Girouard

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Pires, P.W., Dorrance, A.M. (2016). The Effects of Hypertension on Cerebral Artery Structure and Function, and Cerebral Blood Flow. 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_6

Download citation

Publish with us

Policies and ethics

Search

Navigation