Vascular Function

  • Rhian M. Touyz
  • Augusto C. Montezano
  • Clive Rosendorff


The vasculature is a dynamic system that is continually undergoing change by adapting to mechanical, hemodynamic, and humoral changes. Central to these processes are vascular smooth muscle cells (VSMC) that constitute the bulk of the vascular media. VSMCs are regulated by many factors that promote contraction, dilation, growth, fibrosis, calcification, and inflammation, which impact on vascular functional and structural changes. Acute regulation of vascular diameter involves activation/deactivation of the contractile machinery, triggered primarily by an increase in intracellular free calcium concentration. Vasoactive agents, such as Ang II, ET-1, bradykinin, and neurotransmitters, regulate vascular function and in pathological conditions contribute to vascular dysfunction and vascular remodeling. Emerging evidence indicates an important role for reactive oxygen species in the regulation of vascular function. Moreover, factors secreted by adipocytes (adipokines) may directly impact on vascular contraction, dilation, growth, and inflammation. Molecular processes underlying these events are complex and involve small G proteins, phospholipases, protein kinase C, mitogen-activated protein kinases, tyrosine kinases, and RhoA–Rho kinase, among others. This chapter addresses mechanisms regulating vascular function (contraction/dilation) and highlights some processes contributing to vascular structural changes (remodeling). Some important vasoactive agents are described, and implications in vascular dysfunction and cardiovascular disease are discussed.


Nitric Oxide Vascular Smooth Muscle Cell Brain Natriuretic Peptide Atrial Natriuretic Peptide Vascular Remodel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Hill MA, Meininger GA. Arteriolar vascular smooth muscle cells: mechanotransducers in a complex environment. Int J Biochem Cell Biol. 2012;44(9):1505–10.PubMedGoogle Scholar
  2. 2.
    Walsh MP. Vascular smooth muscle myosin light chain diphosphorylation: mechanism, function, and pathological implications. IUBMB Life. 2011;63(11):987–1000.PubMedGoogle Scholar
  3. 3.
    Davis MJ. Perspective: physiological role(s) of the vascular myogenic response. Microcirculation. 2012;19(2):99–114.PubMedGoogle Scholar
  4. 4.
    Sacharidou A, Stratman AN, Davis GE. Molecular mechanisms controlling vascular lumen formation in three-dimensional extracellular matrices. Cells Tissues Organs. 2012;195(1–2):122–43.PubMedGoogle Scholar
  5. 5.
    Tuna BG, Bakker EN, VanBavel E. Smooth muscle biomechanics and plasticity: relevance for vascular calibre and remodelling. Basic Clin Pharmacol Toxicol. 2012;110(1):35–41.PubMedGoogle Scholar
  6. 6.
    Morgado M, Cairrão E, Santos-Silva AJ, Verde I. Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle. Cell Mol Life Sci. 2012;69(2):247–66.PubMedGoogle Scholar
  7. 7.
    Kim HR, Appel S, Vetterkind S, Gangopadhyay SS, Morgan KG. Smooth muscle signalling pathways in health and disease. J Cell Mol Med. 2008;12(6A):2165–80.PubMedGoogle Scholar
  8. 8.
    Quintavalle M, Condorelli G, Elia L. Arterial remodeling and atherosclerosis: miRNAs involvement. Vascul Pharmacol. 2011;55(4):106–10.PubMedGoogle Scholar
  9. 9.
    Matchkov VV, Kudryavtseva O, Aalkjaer C. Intracellular Ca2+ signalling and phenotype of vascular smooth muscle cells. Basic Clin Pharmacol Toxicol. 2012;110(1):42–8.PubMedGoogle Scholar
  10. 10.
    Wang Y, Deng X, Hewavitharana T, Soboloff J, Gill DL. Stim, ORAI and TRPC channels in the control of calcium entry signals in smooth muscle. Clin Exp Pharmacol Physiol. 2008;35(9):1127–33.PubMedGoogle Scholar
  11. 11.
    House SJ, Potier M, Bisaillon J, Singer HA, Trebak M. The non-excitable smooth muscle: calcium signaling and phenotypic switching during vascular disease. Pflugers Arch. 2008;456(5):769–85.PubMedGoogle Scholar
  12. 12.
    Courjaret R, Machaca K. STIM and Orai in cellular proliferation and division. Front Biosci. 2012;4:331–41.Google Scholar
  13. 13.
    Fukami K, Inanobe S, Kanemaru K, Nakamura Y. Phospholipase C is a key enzyme regulating intracellular calcium and modulating the phosphoinositide balance. Prog Lipid Res. 2010;49(4):429–37.PubMedGoogle Scholar
  14. 14.
    Bunney TD, Katan M. PLC regulation: emerging pictures for molecular mechanisms. Trends Biochem Sci. 2011;36(2):88–96.PubMedGoogle Scholar
  15. 15.
    Bastin G, Heximer SP. Intracellular regulation of heterotrimeric G-protein signaling modulates vascular smooth muscle cell contraction. Arch Biochem Biophys. 2011;510(2):182–9.PubMedGoogle Scholar
  16. 16.
    Ushio-Fukai M. Vascular signaling through G protein-coupled receptors: new concepts. Curr Opin Nephrol Hypertens. 2009;18(2):153–9.PubMedGoogle Scholar
  17. 17.
    Ligeti E, Csépányi-Kömi R, Hunyady L. Physiological mechanisms of signal termination in biological systems. Acta Physiol (Oxf). 2012;204(4):469–78.Google Scholar
  18. 18.
    George L, Arnau C, Leonardo P. The G-protein coupled receptor family: actors with many faces. Curr Pharm Des. 2012;18(2):175–85.PubMedGoogle Scholar
  19. 19.
    Nguyen Dinh Cat A, Touyz RM. Cell signaling of angiotensin II on vascular tone: novel mechanisms. Curr Hypertens Rep. 2011;13(2):122–8.PubMedGoogle Scholar
  20. 20.
    Horiuchi M, Iwanami J, Mogi M. Regulation of angiotensin II receptors beyond the classical pathway. Clin Sci (Lond). 2012;123(4):193–203.Google Scholar
  21. 21.
    Johnston-Cox HA, Koupenova M, Ravid K. A2 adenosine receptors and vascular pathologies. Arterioscler Thromb Vasc Biol. 2012;32(4):870–8.PubMedGoogle Scholar
  22. 22.
    Rozengurt E. Mitogenic signaling pathways induced by G protein-coupled receptors. J Cell Physiol. 2007;213(3):589–602.PubMedGoogle Scholar
  23. 23.
    Pradhan S, Sumpio B. Molecular and biological effects of hemodynamics on vascular cells. Front Biosci. 2004;9:3276–85.PubMedGoogle Scholar
  24. 24.
    Erickson JR, He BJ, Grumbach IM, Anderson ME. CaMKII in the cardiovascular system: sensing redox states. Physiol Rev. 2011;91(3):889–915.PubMedGoogle Scholar
  25. 25.
    Konstantinidis G, Moustakas A, Stournaras C. Regulation of myosin light chain function by BMP signaling controls actin cytoskeleton remodeling. Cell Physiol Biochem. 2011;28(5):1031–44.PubMedGoogle Scholar
  26. 26.
    Kaneko-Kawano T, Takasu F, Naoki H, Sakumura Y, Ishii S, Ueba T, et al. Dynamic regulation of myosin light chain phosphorylation by Rho-kinase. PLoS One. 2012;7(6):e39269.PubMedGoogle Scholar
  27. 27.
    Khromov A, Choudhury N, Stevenson AS, Somlyo AV, Eto M. Phosphorylation-dependent autoinhibition of myosin light chain phosphatase accounts for Ca2+ sensitization force of smooth muscle contraction. J Biol Chem. 2009;284(32):21569–79.PubMedGoogle Scholar
  28. 28.
    Wirth A. Rho kinase and hypertension. Biochim Biophys Acta. 2010;1802(12):1276–84.PubMedGoogle Scholar
  29. 29.
    Loirand G, Guerin P, Pacaud P. Rho kinases in cardiovascular physiology and pathophysiology. Circ Res. 2006;98:322–34.PubMedGoogle Scholar
  30. 30.
    Loirand G, Pacaud P. The role of Rho protein signaling in hypertension. Nat Rev Cardiol. 2010;7(11):637–47.PubMedGoogle Scholar
  31. 31.
    Chuang HH, Yang CH, Tsay YG, Hsu CY, Tseng LM, Chang ZF, et al. ROCKII Ser1366 phosphorylation reflects the activation status. Biochem J. 2012;443(1):145–51.PubMedGoogle Scholar
  32. 32.
    Bagi Z, Feher A, Cassuto J, Akula K, Labinskyy N, Kaley G, et al. Increased availability of angiotensin AT 1 receptors leads to sustained arterial constriction to angiotensin II in diabetes – role for Rho-kinase activation. Br J Pharmacol. 2011;163(5):1059–68.PubMedGoogle Scholar
  33. 33.
    Seyler C, Duthil-Straub E, Zitron E, Gierten J, Scholz EP, Fink RH, et al. TASK1 (K(2P)3.1) K(+) channel inhibition by endothelin-1 is mediated through Rho kinase-dependent phosphorylation. Br J Pharmacol. 2012;165(5):1467–75.PubMedGoogle Scholar
  34. 34.
    Montezano AC, Callera GE, Yogi A, He Y, Tostes RC, He G, et al. Aldosterone and angiotensin II synergistically stimulate migration in vascular smooth muscle cells through c-Src-regulated redox-sensitive RhoA pathways. Arterioscler Thromb Vasc Biol. 2008;28(8):1511–18.PubMedGoogle Scholar
  35. 35.
    Fujimura N, Noma K, Hata T, Soga J, Hidaka T, Idei N, et al. Mineralocorticoid receptor blocker eplerenone improves endothelial function and inhibits Rho-associated kinase activity in patients with hypertension. Clin Pharmacol Ther. 2012;91(2):289–97.PubMedGoogle Scholar
  36. 36.
    Uehata M. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997;389(6654):990–4.PubMedGoogle Scholar
  37. 37.
    Surma M, Wei L, Shi J. Rho kinase as a therapeutic target in cardiovascular disease. Future Cardiol. 2011;7(5):657–71.PubMedGoogle Scholar
  38. 38.
    Satoh K, Fukumoto Y, Shimokawa H. Rho-kinase: important new therapeutic target in cardiovascular diseases. Am J Physiol Heart Circ Physiol. 2011;301(2):H287–96.PubMedGoogle Scholar
  39. 39.
    Velat GJ, Kimball MM, Mocco JD, Hoh BL. Vasospasm after aneurysmal subarachnoid hemorrhage: review of randomized controlled trials and meta-analyses in the literature. World Neurosurg. 2011;76(5):446–54.PubMedGoogle Scholar
  40. 40.
    Marchand A, Abi-Gerges A, Saliba Y, Merlet E, Lompré AM. Calcium signaling in vascular smooth muscle cells: from physiology to pathology. Adv Exp Med Biol. 2012;740:795–810.PubMedGoogle Scholar
  41. 41.
    Pagiatakis C, Gordon JW, Ehyai S, McDermott JC. A novel RhoA/ROCK-CPI-17-MEF2C signaling pathway regulates vascular smooth muscle cell gene expression. J Biol Chem. 2012;287(11):8361–70.PubMedGoogle Scholar
  42. 42.
    Schapira AH. Monoamine oxidase B inhibitors for the treatment of Parkinson’s disease: a review of symptomatic and potential disease-modifying effects. CNS Drugs. 2011;25(12):1061–71.PubMedGoogle Scholar
  43. 43.
    Lymperopoulos A. Beta-arrestin biased agonism/antagonism at cardiovascular seven transmembrane-spanning receptors. Curr Pharm Des. 2012;18(2):192–8.PubMedGoogle Scholar
  44. 44.
    Zeng C, Jose PA. Dopamine receptors: important antihypertensive counterbalance against hypertensive factors. Hypertension. 2011;57(1):11–7.PubMedGoogle Scholar
  45. 45.
    Nguyen Dinh Cat A, Touyz RM. A new look at the renin-angiotensin system-focusing on the vascular system. Peptides. 2011;32(10):2141–50.PubMedGoogle Scholar
  46. 46.
    Gwathmey TM, Alzayadneh EM, Pendergrass KD, Chappell MC. Novel roles of nuclear angiotensin receptors and signaling mechanisms. Am J Physiol Regul Integr Comp Physiol. 2012;302(5):R518–30.PubMedGoogle Scholar
  47. 47.
    Rosendorff C. The renin-angiotensin system and vascular hypertrophy. J Am Coll Cardiol. 1996;28:803–12.PubMedGoogle Scholar
  48. 48.
    Benigni A, Cassis P, Remuzzi G. Angiotensin II revisited: new roles in inflammation, immunology and aging. EMBO Mol Med. 2010;2(7):247–57.PubMedGoogle Scholar
  49. 49.
    Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol. 2007;292(1):C82–97.PubMedGoogle Scholar
  50. 50.
    Lemarié CA, Schiffrin EL. The angiotensin II type 2 receptor in cardiovascular disease. J Renin Angiotensin Aldosterone Syst. 2010;11(1):19–31.PubMedGoogle Scholar
  51. 51.
    Touyz RM, Schiffrin EL. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacol Rev. 2000;52:639–72.PubMedGoogle Scholar
  52. 52.
    Touyz RM, Schiffrin EL. Increased generation of superoxide by angiotensin II in smooth muscle cells from resistance arteries of hypertensive patients: role of phospholipase D-dependent NAD(P)H oxidase-sensitive pathways. J Hypertens. 2001;19(7):1245–54.PubMedGoogle Scholar
  53. 53.
    Imig JD. Epoxides and soluble epoxide hydrolase in cardiovascular physiology. Physiol Rev. 2012;92(1):101–30.PubMedGoogle Scholar
  54. 54.
    Stegbauer J, Coffman TM. New insights into angiotensin receptor actions: from blood pressure to aging. Curr Opin Nephrol Hypertens. 2011;20(1):84–8.PubMedGoogle Scholar
  55. 55.
    Ohtsu H, Suzuki H, Nakashima H, Dhobale S, Frank GD, Motley ED, et al. Angiotensin II signal transduction through small GTP-binding proteins: mechanism and significance in vascular smooth muscle cells. Hypertension. 2006;48(4):534–40.PubMedGoogle Scholar
  56. 56.
    Mederosy Schnitzler M, Storch U, Gudermann T. AT1 receptors as mechanosensors. Curr Opin Pharmacol. 2011;11(2):112–16.Google Scholar
  57. 57.
    Rautureau Y, Schiffrin EL. Endothelin in hypertension: an update. Curr Opin Nephrol Hypertens. 2012;21(2):128–36.PubMedGoogle Scholar
  58. 58.
    Guilluy C, Bregeon J, Tourmaniantz G. The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure. Nat Med. 2010;16:183–90.PubMedGoogle Scholar
  59. 59.
    Garrido AM, Griendling KK. NADPH oxidases and angiotensin II receptor signaling. Mol Cell Endocrinol. 2009;302(2):148–58.PubMedGoogle Scholar
  60. 60.
    Rosendorff C. Endothelin, vascular hypertrophy and hypertension. Cardiovasc Drugs Ther. 1996;10:795–802.Google Scholar
  61. 61.
    Davenport AP, Maguire JJ. Pharmacology of renal endothelin receptors. Contrib Nephrol. 2011;172:1–17.PubMedGoogle Scholar
  62. 62.
    Rodríguez-Pascual F, Busnadiego O, Lagares D, Lamas S. Role of endothelin in the cardiovascular system. Pharmacol Res. 2011;63(6):463–72.PubMedGoogle Scholar
  63. 63.
    Jandeleit-Dahm KA, Watson AM. The endothelin system and endothelin receptor antagonists. Curr Opin Nephrol Hypertens. 2012;21(1):66–71.PubMedGoogle Scholar
  64. 64.
    Lima VV, Giachini FR, Hardy DM, Webb RC, Tostes RC. O-GlcNAcylation: a novel pathway contributing to the effects of endothelin in the vasculature. Am J Physiol Regul Integr Comp Physiol. 2011;300(2):R236–50.PubMedGoogle Scholar
  65. 65.
    Ivey ME, Osman N, Little PJ. Endothelin-1 signalling in vascular smooth muscle: pathways controlling cellular functions associated with atherosclerosis. Atherosclerosis. 2008;199(2):237–47.PubMedGoogle Scholar
  66. 66.
    Bourque SL, Davidge ST, Adams MA. The interaction between endothelin-1 and nitric oxide in the vasculature: new perspectives. Am J Physiol Regul Integr Comp Physiol. 2011;300(6):R1288–95.PubMedGoogle Scholar
  67. 67.
    Dhaun N, Goddard J, Webb DJ. Endothelin antagonism in patients with nondiabetic chronic kidney disease. Contrib Nephrol. 2011;172:243–54.PubMedGoogle Scholar
  68. 68.
    Lazich I, Bakris GL. Endothelin antagonism in patients with resistant hypertension and hypertension nephropathy. Contrib Nephrol. 2011;172:223–34.PubMedGoogle Scholar
  69. 69.
    Fligny C, Barton M, Tharaux PL. Endothelin and podocyte injury in chronic kidney disease. Contrib Nephrol. 2011;172:120–38.PubMedGoogle Scholar
  70. 70.
    Ergul A. Endothelin-1 and diabetic complications: focus on the vasculature. Pharmacol Res. 2011;63(6):477–82.PubMedGoogle Scholar
  71. 71.
    Schiffrin EL. Vascular endothelin in hypertension. Vascul Pharmacol. 2005;43(1):19–29.PubMedGoogle Scholar
  72. 72.
    Berrazueta JR, Bhagat K, Vallance P, MacAllister RJ. Dose- and time-dependency of the dilator effects of the endothelin antagonist, BQ-123, in the human forearm. Br J Clin Pharmacol. 1997;44:569–71.PubMedGoogle Scholar
  73. 73.
    Haynes WG, Hand M, Johnstone H, Padfield P, Webb DJ. Direct and sympathetically mediated venoconstriction in essential hypertension: enhanced response to endothelin-1. J Clin Invest. 1994;94:1359–64.PubMedGoogle Scholar
  74. 74.
    McCulloch KM, Docherty CC, Morecroft I, et al. Endothelin B receptor-mediated contraction in human pulmonary resistance arteries. Br J Pharmacol. 1996;119:1125–30.PubMedGoogle Scholar
  75. 75.
    Sikkeland LI, Dahl CP, Ueland T, Andreassen AK, Gude E, Edvardsen T, et al. Increased levels of inflammatory cytokines and endothelin-1 in alveolar macrophages from patients with chronic heart failure. PLoS One. 2012;7(5):e36815.PubMedGoogle Scholar
  76. 76.
    Vernerová Z, Kujal P, Kramer HJ, Bäcker A, Cervenka L, Vanecková I. End-organ damage in hypertensive transgenic Ren-2 rats: influence of early and late endothelin receptor blockade. Physiol Res. 2009;58:S69–78.PubMedGoogle Scholar
  77. 77.
    Rich S, McLaughlin VV. Endothelin receptor blockers in cardiovascular disease. Circulation. 2003;108(18):2184–90.PubMedGoogle Scholar
  78. 78.
    Black HR, Bakris GL, Weber MA, Weiss R, Shahawy ME, Marple R, et al. Efficacy and safety of darusentan in patients with resistant hypertension: results from a randomized, double-blind, placebo-controlled dose-ranging study. J Clin Hypertens (Greenwich). 2007;9(10):760–9.Google Scholar
  79. 79.
    Anand I, McMurray J, Cohn JN, Konstam MA, Notter T, Quitzau K, et al. Long-term effects of darusentan on left-ventricular remodelling and clinical outcomes in the EndothelinA Receptor Antagonist Trial in Heart Failure (EARTH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364(9431):347–54.PubMedGoogle Scholar
  80. 80.
    Westfall TC, Westfall DP. Neurotransmission – the autonomic and somatic nervous systems. In: Brunton LL, Chabner BA, Knollman BC, editors. Goodman and Gilman’s the pharmacologic basis of therapeutics. 12th ed. New York: McGraw Hill; 2011. p. 171–218.Google Scholar
  81. 81.
    Watts SW, Davis RP. 5-hydroxtryptamine receptors in systemic hypertension: an arterial focus. Cardiovasc Ther. 2011;29(1):54–67.PubMedGoogle Scholar
  82. 82.
    Riksen NP, Rongen GA. Targeting adenosine receptors in the development of cardiovascular therapeutics. Expert Rev Clin Pharmacol. 2012;5(2):199–218.PubMedGoogle Scholar
  83. 83.
    Hauck C, Frishman WH. Systemic hypertension: the roles of salt, vascular Na+/K+ ATPase and the endogenous glycosides, ouabain and marinobufagenin. Cardiol Rev. 2012;20(3):130–8.PubMedGoogle Scholar
  84. 84.
    Pfister SL, Gauthier KM, Campbell WB. Vascular pharmacology of epoxyeicosatrienoic acids. Adv Pharmacol. 2010;60:27–59.PubMedGoogle Scholar
  85. 85.
    Maurer M, Bader M, Bas M, Bossi F, Cicardi M, Cugno M, et al. New topics in bradykinin research. Allergy. 2011;66(11):1397–406.PubMedGoogle Scholar
  86. 86.
    Costa MA, Arranz CT. New aspects of the interactions between the cardiovascular nitric oxide system and natriuretic peptides. Biochem Biophys Res Commun. 2011;406(2):161–4.PubMedGoogle Scholar
  87. 87.
    de Bold AJ. Thirty years of research on atrial natriuretic factor: historical background and emerging concepts. Can J Physiol Pharmacol. 2011;89(8):527–31.PubMedGoogle Scholar
  88. 88.
    Cowley AW, Michalkiewiz M. Vasopressin and neuropeptide Y. In: Izzo JL, Sica DA, Black HR, editors. Hypertension primer. 4th ed. Philadelphia: American Heart Association and Lippincott Williams & Wilkins; 2008. p. 70–3.Google Scholar
  89. 89.
    RS A, Flier JS. Adipose tissue as an endocrine organ. Trends Endocrinol Metab. 2000;11:327–33.Google Scholar
  90. 90.
    Xu A, Vanhoutte PM. Adiponectin and adipocyte fatty acid binding protein in the pathogenesis of cardiovascular disease. Am J Physiol Heart Circ Physiol. 2012;302(6):H1231–40.PubMedGoogle Scholar
  91. 91.
    Szasz T, Webb RC. Perivascular adipose tissue: more than just structural support. Clin Sci (Lond). 2012;122(1):1–12.Google Scholar
  92. 92.
    Briones AM, Cat AN, Callera GE, Yogi A, Burger D, He Y, et al. Adipocytes produce aldosterone through calcineurin-dependent signaling pathways: implications in diabetes mellitus-associated obesity and vascular dysfunction. Hypertension. 2012;59(5):1069–78.PubMedGoogle Scholar
  93. 93.
    Nguyen Dinh Cat A, Briones AM, Callera GE, Yogi A, He Y, Montezano AC, et al. Adipocyte-derived factors regulate vascular smooth muscle cells through mineralocorticoid and glucocorticoid receptors. Hypertension. 2011;58(3):479–88.PubMedGoogle Scholar
  94. 94.
    Vaughn DE. Plasminogen activator inhibitor-1: a common denominator in cardiovascular disease. J Invest Med. 1998;46:370–6.Google Scholar
  95. 95.
    Bishop-Bailey D. Peroxisome proliferator-activated receptors in the cardiovascular system. Br J Pharmacol. 2000;129:823–34.PubMedGoogle Scholar
  96. 96.
    Kietadisorn R, Juni RP, Moens AL. Tackling endothelial dysfunction by modulating NOS uncoupling: new insights into its pathogenesis and therapeutic possibilities. Am J Physiol Endocrinol Metab. 2012;302(5):E481–95.PubMedGoogle Scholar
  97. 97.
    Cunnington C, Van Assche T, Shirodaria C, Kylintireas I, Lindsay AC, Lee JM, et al. Systemic and vascular oxidation limits the efficacy of oral tetrahydrobiopterin treatment in patients with coronary artery disease. Circulation. 2012;125(11):1356–66.PubMedGoogle Scholar
  98. 98.
    Montezano AC, Touyz RM. Reactive oxygen species and endothelial function–role of nitric oxide synthase uncoupling and Nox family nicotinamide adenine dinucleotide phosphate oxidases. Basic Clin Pharmacol Toxicol. 2012;110(1):87–94.PubMedGoogle Scholar
  99. 99.
    Al Ghouleh I, Khoo NK, Knaus UG, Griendling KK, Touyz RM, Thannickal VJ, et al. Oxidases and peroxidases in cardiovascular and lung disease: new concepts in reactive oxygen species signaling. Free Radic Biol Med. 2011;51(7):1271–8.PubMedGoogle Scholar
  100. 100.
    Brown DI, Griendling KK. Nox proteins in signal transduction. Free Radic Biol Med. 2009;47(9):1239–53.PubMedGoogle Scholar
  101. 101.
    Montezano AC, Burger D, Ceravolo GS, Yusuf H, Montero M, Touyz RM. Novel Nox homologues in the vasculature: focusing on Nox4 and Nox5. Clin Sci (Lond). 2011;120(4):131–41.Google Scholar
  102. 102.
    Harrison DG, Chen W, Dikalov S, Li L. Regulation of endothelial cell tetrahydrobiopterin pathophysiological and therapeutic implications. Adv Pharmacol. 2010;60:107–32.PubMedGoogle Scholar
  103. 103.
    Touyz RM, Briones AM, Sedeek M, Burger D, Montezano AC. NOX isoforms and reactive oxygen species in vascular health. Mol Interv. 2011;11(1):27–35.PubMedGoogle Scholar
  104. 104.
    Savoia C, Burger D, Nishigaki N, Montezano A, Touyz RM. Angiotensin II and the vascular phenotype in hypertension. Expert Rev Mol Med. 2011;13:e1.Google Scholar
  105. 105.
    Batchu SN, Korshunov VA. Novel tyrosine kinase signaling pathways: implications in vascular remodeling. Curr Opin Nephrol Hypertens. 2012;21(2):122–7.PubMedGoogle Scholar
  106. 106.
    Inoue T, Croce K, Morooka T, Sakuma M, Node K, Simon DI. Vascular inflammation and repair: implications for re-endothelialization, restenosis, and stent thrombosis. JACC Cardiovasc Interv. 2011;4(10):1057–66.PubMedGoogle Scholar
  107. 107.
    Korshunov VA, Berk BC. Smooth muscle apoptosis and vascular remodeling. Curr Opin Hematol. 2008;15(3):250–5.PubMedGoogle Scholar
  108. 108.
    Schiffrin EL. T lymphocytes: a role in hypertension? Curr Opin Nephrol Hypertens. 2010;19(2):181–6.PubMedGoogle Scholar
  109. 109.
    Hassoun PM, Mouthon L, Barberà JA, Eddahibi S, Flores SC, Grimminger F, et al. Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol. 2009;54(1 Suppl):S10–19.PubMedGoogle Scholar
  110. 110.
    Schiffrin EL. Immune modulation of resistance artery remodelling. Basic Clin Pharmacol Toxicol. 2012;110(1):70–2.PubMedGoogle Scholar
  111. 111.
    Edwards G, Félétou M, Weston AH. Endothelium-derived hyperpolarising factors and associated pathways: a synopsis. Pflugers Arch. 2010;459(6):863–7.PubMedGoogle Scholar
  112. 112.
    Zape JP, Zovein AC. Hemogenic endothelium: origins, regulation, and implications for vascular biology. Semin Cell Dev Biol. 2011;22(9):1036–47.PubMedGoogle Scholar
  113. 113.
    Burger D, Montezano AC, Nishigaki N, He Y, Carter A, Touyz RM. Endothelial microparticle formation by angiotensin II is mediated via Ang II receptor type I/NADPH oxidase/Rho kinase pathways targeted to lipid rafts. Arterioscler Thromb Vasc Biol. 2011;31(8):1898–907.PubMedGoogle Scholar
  114. 114.
    Burger D, Touyz RM. Cellular biomarkers of endothelial health: microparticles, endothelial progenitor cells, and circulating endothelial cells. J Am Soc Hypertens. 2012;6(2):85–99.PubMedGoogle Scholar

Recommended Reading

  1. Alexander MR, Owens GK. Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease. Annu Rev Physiol. 2012;74:13–40.PubMedGoogle Scholar
  2. Heagerty AM, Heerkens EH, Izzard AS. Small artery structure and function in hypertension. J Cell Mol Med. 2010;14(5):1037–43.PubMedGoogle Scholar
  3. Hill MA, Meininger GA. Arteriolar vascular smooth muscle cells: mechanotransducers in a complex environment. Int J Biochem Cell Biol. 2012;44(9):1505–10.PubMedGoogle Scholar
  4. Martinez-Lemus LA, Hill MA, Meininger GA. The plastic nature of the vascular wall: a continuum of remodeling events contributing to control of arteriolar diameter and structure. Physiology (Bethesda). 2009;24:45–57.Google Scholar
  5. Walsh MP, Kargacin GJ, Kendrick-Jones J, Lincoln TM. Intracellular mechanisms involved in the regulation of vascular smooth muscle tone. Can J Physiol Pharmacol. 1995;73(5):565–73.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Rhian M. Touyz
    • 1
  • Augusto C. Montezano
    • 1
  • Clive Rosendorff
    • 2
  1. 1.Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research CentreUniversity of GlasgowGlasgowUK
  2. 2.Department of MedicineThe Mount Sinai School of Medicine, The James J. Peters VA Medical CenterBronxUSA

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