Cellular and Ionic Mechanisms of Arterial Vasomotion

  • William C. ColeEmail author
  • Grant R. Gordon
  • Andrew P. Braun
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1124)


Rhythmical contractility of blood vessels was first observed in bat wing veins by Jones (Philos Trans R Soc Lond 1852:142, 131–136), and subsequently described in arteries and arterioles of multiple vascular beds in several species. Despite an abundance of descriptive literature regarding the presence of vasomotion, to date we do not have an accurate picture of the cellular and ionic basis of these oscillations in tone, or the physiological relevance of the changes in pulsatile blood flow arising from vasomotion. This chapter reviews our current understanding of the cellular and ionic mechanisms underlying vasomotion in resistance arteries and arterioles. Focus is directed to the ion channels, changes in cytosolic Ca2+ concentration, and involvement of intercellular gap junctions in the development and synchronization of rhythmic changes in membrane potential and cytosolic Ca2+ concentration within the vessel wall that contribute to vasomotion. The physiological consequences of vasomotion are discussed with a focus on the cerebral vasculature, as recent advances show that rhythmic oscillations in cerebral arteriolar diameter appear to be entrained by cortical neural activity to increase the local supply of blood flow to active regions of the brain.


Vasomotion Artery Arteriole Vascular smooth muscle Endothelium Sympathetic nerve Neurovascular coupling 



The authors thank Drs. HL Zhu and XZ Zhong for the original recordings of vasomotion presented in Fig. 12.1. The work is supported by a research operating grant from the Canadian Institutes of Health Research (PJT-155963).


  1. 1.
    Jones TW. Discovery that veins of the bat’s wing (which are furnished with valves) are endowed with rhythmical contractility and that the onward flow of blood is accelerated by each contraction. Philos Trans R Soc Lond. 1852;142:131–6.CrossRefGoogle Scholar
  2. 2.
    Funk W, Intaglietta M. Spontaneous arteriolar vasomotion. Prog Appl Microcirc. 1983;3:66–82.CrossRefGoogle Scholar
  3. 3.
    Shimamura K, Sekiguchi F, Sunano S. Tension oscillation in arteries and its abnormality in hypertensive animals. Clin Exp Pharmacol Physiol. 1999;26:275–84.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Nilsson H, Aalkjaer C. Vasomotion: mechanisms and physiological importance. Mol Interv. 2003;3:79–89.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Aalkjaer C, Nilsson H. Vasomotion: cellular background for the oscillator and for the synchronization of smooth muscle cells. Br J Pharmacol. 2005;144:605–16.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Haddock RE, Hill CE. Rhythmicity in arterial smooth muscle. J Physiol. 2005;566:645–56.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Aalkjaer C, Boedtkjer D, Matchkov V. Vasomotion—what is currently thought? Acta Physiol (Oxford). 2011;202:253–69.CrossRefGoogle Scholar
  8. 8.
    Matchkov VV. Mechanisms of cellular synchronization in the vascular wall. Mechanisms of vasomotion. Dan Med Bull. 2010;57:B4191.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Intaglietta M. Vasomotion and flowmotion: physiological mechanisms and clinical evidence. Vasc Med Rev. 1990;1:101–12.CrossRefGoogle Scholar
  10. 10.
    Schmidt JA. Periodic hemodynamics in health and disease. Georgetown, TX: R.G. Landes Company; 1996.Google Scholar
  11. 11.
    Kvandal P, Landsverk SA, Bernjak A, Stefanovska A, Kvernmo HD, Kirkebøen KA. Low-frequency oscillations of the laser Doppler perfusion signal in human skin. Microvasc Res. 2006;72:120–7.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Stefanovska A. Coupled oscillators. Complex but not complicated cardiovascular and brain interactions. IEEE Eng Med Biol Mag. 2007;26:25–9.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Gokina NI, Bevan RD, Walters CL, Bevan JA. Electrical activity underlying rhythmic contraction in human pial arteries. Circ Res. 1996;78:148–53.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Mateo C, Knutsen PM, Tsai PS, Shih AY, Kleinfeld D. Entrainment of arteriole vasomotor fluctuations by neural activity is a basis of blood-oxygenation-level-dependent “resting-state” connectivity. Neuron. 2017;96:936–48.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Mauban JR, Lamont C, Balke CW, Wier WG. Adrenergic stimulation of rat resistance arteries affects Ca2+ sparks, Ca2+ waves, and Ca2+ oscillations. Am J Physiol Heart Circ Physiol. 2001;280:H2399–405.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Peng H, Matchkov V, Ivarsen A, Aalkjaer C, Nilsson H. Hypothesis for the initiation of vasomotion. Circ Res. 2001;88:810–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Oishi H, Schuster A, Lamboley M, Stergiopulos N, Meister JJ, Bény JL. Role of membrane potential in vasomotion of isolated pressurized rat arteries. Life Sci. 2002;71:2239–48.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Zacharia J, Zhang J, Wier WG. Ca2+ signaling in mouse mesenteric small arteries: myogenic tone and adrenergic vasoconstriction. Am J Physiol Heart Circ Physiol. 2007;292(3):H1523–32.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Haddock RE, Hirst GD, Hill CE. Voltage independence of vasomotion in isolated irideal arterioles of the rat. J Physiol. 2002;540:219–29.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Bakker EN, Sorop O, Spaan JA, VanBavel E. Remodeling of resistance arteries in organoid culture is modulated by pressure and pressure pulsation and depends on vasomotion. Am J Physiol Heart Circ Physiol. 2004;286:H2052–6.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Colantuoni A, Bertuglia S, Intaglietta M. Quantitation of rhythmic diameter changes in arterial microcirculation. Am J Phys. 1984;246:H508–17.Google Scholar
  22. 22.
    Fairfax ST, Mauban JR, Hao S, Rizzo MA, Zhang J, Wier WG. Ca2+ signaling in arterioles and small arteries of conscious, restrained, optical biosensor mice. Front Physiol. 2014;5:387.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Griffith TM, Edwards DH. Mechanisms underlying chaotic vasomotion in isolated resistance arteries: roles of calcium and EDRF. Biorheology. 1993;30:333–47.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Griffith TM, Edwards DH. Ca2+ sequestration as a determinant of chaos and mixed-mode dynamics in agonist-induced vasomotion. Am J Phys. 1997;272:H1696–709.Google Scholar
  25. 25.
    Colantuoni A, Bertuglia S, Intaglietta M. Variations of rhythmic diameter changes at the arterial micro-vascular bifurcations. Pflugers Arch. 1985;403:289–95.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Oude Vrielink HHE, Slaaf DW, Tangelder GJ, Weijmer-Van Velzen S, Reneman RR. Analysis of vasomotion waveform changes during pressure reduction and adenosine application. Am J Phys. 1990;258:H29–37.Google Scholar
  27. 27.
    Gustafsson H. Vasomotion and underlying mechanisms in small arteries. An in vitro study of rat blood vessels. Acta Physiol Scand. 1993;149(Suppl. 614):1–44.Google Scholar
  28. 28.
    Nyvad J, Mazur A, Postnov DD, Straarup MS, Soendergaard AM, Staehr C, Brøndum E, Aalkjaer C, Matchkov VV. Intravital investigation of rat mesenteric small artery tone and blood flow. J Physiol. 2017;595:5037–53.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Burrows ME, Johnson PC. Diameter, wall tension, and flow in mesenteric arterioles during autoregulation. Am J Phys. 1981;241:H829–37.Google Scholar
  30. 30.
    Hundley WG, Renaldo GJ, Levasseur JE, Kontos HA. Vasomotion in cerebral microcirculation of awake rabbits. Am J Phys. 1988;254:H67–71.Google Scholar
  31. 31.
    Drew PJ, Shih AY, Kleinfeld D. Fluctuating and sensory-induced vasodynamics in rodent cortex extend arteriole capacity. Proc Natl Acad Sci U S A. 2011;108:8473–8.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Mauban JR, Fairfax ST, Rizzo MA, Zhang J, Wier WG. A method for noninvasive longitudinal measurements of [Ca2+] in arterioles of hypertensive optical biosensor mice. Am J Physiol Heart Circ Physiol. 2014;307:H173–81.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Matchkov VV, Larsen P, Bouzinova EV, Rojek A, Boedtkjer DM, Golubinskaya V, Pedersen FS, Aalkjaer C, Nilsson H. Bestrophin-3 (vitelliform macular dystrophy 2-like 3 protein) is essential for the cGMP-dependent calcium-activated chloride conductance in vascular smooth muscle cells. Circ Res. 2008;103:864–72.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Broegger T, Jacobsen JC, Secher Dam V, Boedtkjer DM, Kold-Petersen H, Pedersen FS, Aalkjaer C, Matchkov VV. Bestrophin is important for the rhythmic but not the tonic contraction in rat mesenteric small arteries. Cardiovasc Res. 2011;91:685–93.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Dam VS, Boedtkjer DM, Nyvad J, Aalkjaer C, Matchkov V. TMEM16A knockdown abrogates two different Ca2+-activated Cl currents and contractility of smooth muscle in rat mesenteric small arteries. Pflugers Arch. 2014;466:1391–409.PubMedCrossRefGoogle Scholar
  36. 36.
    Mauban JR, Zacharia J, Zhang J, Wier WG. Vascular tone and Ca2+ signaling in murine cremaster muscle arterioles in vivo. Microcirculation. 2013;220:269–77.CrossRefGoogle Scholar
  37. 37.
    Westcott EB, Segal SS. Perivascular innervation: a multiplicity of roles in vasomotor control and myoendothelial signaling. Microcirculation. 2013;20:217–38.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Haddock RE, Grayson TH, Brackenbury TD, Meaney KR, Neylon CB, Sandow SL, Hill CE. Endothelial coordination of cerebral vasomotion via myoendothelial gap junctions containing connexins 37 and 40. Am J Physiol Heart Circ Physiol. 2006;291:H2047–56.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Sandow SL, Senadheera S, Bertrand PP, Murphy TV, Tare M. Myoendothelial contacts, gap junctions, and microdomains: anatomical links to function? Microcirculation. 2012;19:403–15.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    de Wit C, Griffith TM. Connexins and gap junctions in the EDHF phenomenon and conducted vasomotor responses. Pflugers Arch. 2010;459:897–914.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Chaytor AT, Evans WH, Griffith TM. Peptides homologous to extracellular loop motifs of connexin 43 reversibly abolish rhythmic contractile activity in rabbit arteries. J Physiol. 1997;503:99–110.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    de Wit C, Roos F, Bolz SS, Pohl U. Lack of vascular connexin 40 is associated with hypertension and irregular arteriolar vasomotion. Physiol Genomics. 2003;13:169–77.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Tsai ML, Watts SW, Loch-Caruso R, Webb RC. The role of gap junctional communication in contractile oscillations in arteries from normotensive and hypertensive rats. J Hypertens. 1995;13:1123–33.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Matchkov VV, Rahman A, Peng H, Nilsson H, Aalkjaer C. Junctional and nonjunctional effects of heptanol and glycyrrhetinic acid derivates in rat mesenteric small arteries. Br J Pharmacol. 2004;142:961–72.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Imtiaz MS, von der Weid PY, van Helden DF. Synchronization of Ca2+ oscillations: a coupled oscillator-based mechanism in smooth muscle. FEBS J. 2010;277:278–85.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Berridge MJ. Smooth muscle cell calcium activation mechanisms. J Physiol. 2008;586:5047–61.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Hill-Eubanks DC, Werner ME, Heppner TJ, Nelson MT. Calcium signaling in smooth muscle. Cold Spring Harb Perspect Biol. 2011;3:a004549.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Missiaen L, Taylor CW, Berridge MJ. Luminal Ca2+ promoting spontaneous Ca2+ release from inositol trisphosphate-sensitive stores in rat hepatocytes. J Physiol. 1992;455:623–40.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Mulvany MJ, Nilsson H, Flatman JA. Role of membrane potential in the response of rat small mesenteric arteries to exogenous noradrenaline stimulation. J Physiol. 1982;332:363–73.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Segal SS, Beny JL. Intracellular recording and dye transfer in arterioles during blood flow control. Am J Phys. 1992;263:H1–7.Google Scholar
  51. 51.
    von der Weid PY, Bény JL. Simultaneous oscillations in the membrane potential of pig coronary artery endothelial and smooth muscle cells. J Physiol. 1993;471:13–24.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Bartlett IS, Crane GJ, Neild TO, Segal SS. Electrophysiological basis of arteriolar vasomotion in vivo. J Vasc Res. 2000;37:568–75.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Haddock RE, Hill CE. Differential activation of ion channels by inositol 1,4,5-trisphosphate IP3- and ryanodine-sensitive calcium stores in rat basilar artery vasomotion. J Physiol. 2002;545:615–27.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Hill CE, Eade J, Sandow SL. Mechanisms underlying spontaneous rhythmical contractions in irideal arterioles of the rat. J Physiol. 1999;521:507–16.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Bouskela E, Grampp W. Spontaneous vasomotion in hamster cheek pouch arterioles in varying experimental conditions. Am J Phys. 1992;262:H478–85.Google Scholar
  56. 56.
    Isotani E, Zhi G, Lau KS, Huang J, Mizuno Y, Persechini A, Geguchadze R, Kamm KE, Stull JT. Real-time evaluation of myosin light chain kinase activation in smooth muscle tissues from a transgenic calmodulin-biosensor mouse. Proc Natl Acad Sci U S A. 2004;101:6279–84.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Ding HL, Ryder JW, Stull JT, Kamm KE. Signaling processes for initiating smooth muscle contraction upon neural stimulation. J Biol Chem. 2009;284:15541–8.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Gustafsson H, Nilsson H. 1993. Rhythmic contractions of isolated small arteries from rat: role of calcium. Acta Physiol Scand. 1993;149:283–91.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Gustafsson H, Mulvany MJ, Nilsson H. Rhythmic contractions of isolated small arteries from rat: influence of the endothelium. Acta Physiol Scand. 1993;143:153–63.CrossRefGoogle Scholar
  60. 60.
    Lamont C, Wier WG. Different roles of ryanodine receptors and inositol (1,4,5)-trisphosphate receptors in adrenergically stimulated contractions of small arteries. Am J Physiol Heart Circ Physiol. 2004;287:H617–25.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Rahman A, Hughes A, Matchkov V, Nilsson H, Aalkjaer C. Antiphase oscillations of endothelium and smooth muscle [Ca2+]i in vasomotion of rat mesenteric small arteries. Cell Calcium. 2007;42:536–47.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Omote M, Mizusawa H. The role of sarcoplasmic reticulum in endothelium-dependent and endothelium-independent rhythmic contractions in the rabbit mesenteric artery. Acta Physiol Scand. 1993;149:15–21.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Westcott EB, Jackson WF. Heterogeneous function of ryanodine receptors, but not IP3 receptors, in hamster cremaster muscle feed arteries and arterioles. Am J Physiol Heart Circ Physiol. 2011;300:H1616–30.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Westcott EB, Goodwin EL, Segal SS, Jackson WF. Function and expression of ryanodine receptors and inositol 1,4,5-trisphosphate receptors in smooth muscle cells of murine feed arteries and arterioles. J Physiol. 2012;590:1849–69.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Matchkov VV, Aalkjaer C, Nilsson H. A cyclic GMP-dependent calcium-activated chloride current in smooth-muscle cells from rat mesenteric resistance arteries. J Gen Physiol. 2004;123:121–34.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Manoury B, Tamuleviciute A, Tammaro P. TMEM16A/anoctamin 1 protein mediates calcium-activated chloride currents in pulmonary arterial smooth muscle cells. J Physiol. 2010;588:2305–14.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Thomas-Gatewood C, Neeb ZP, Bulley S, Adebiyi A, Bannister JP, Leo MD, Jaggar JH. TMEM16A channels generate Ca2+-activated Cl currents in cerebral artery smooth muscle cells. Am J Phys. 2011;301:H1819–27.Google Scholar
  68. 68.
    Adebiyi A, Zhao G, Narayanan D, Thomas-Gatewood CM, Bannister JP, Jaggar JH. Isoform-selective physical coupling of TRPC3 channels to IP3 receptors in smooth muscle cells regulates arterial contractility. Circ Res. 2010;106:1603–12.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Gonzales AL, Amberg GC, Earley S. Ca2+ release from the sarcoplasmic reticulum is required for sustained TRPM4 activity in cerebral artery smooth muscle cells. Am J Phys Cell Phys. 2010;299:C279–88.CrossRefGoogle Scholar
  70. 70.
    Gonzales AL, Yang Y, Sullivan MN, Sanders L, Dabertrand F, Hill-Eubanks DC, Nelson MT, Earley S. A PLCγ1-dependent, force-sensitive signaling network in the myogenic constriction of cerebral arteries. Sci Signal. 2014;7:ra49.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Chen X, Yang D, Ma S, He H, Luo Z, Feng X, Cao T, Ma L, Yan Z, Liu D, Tepel M, Zhu Z. Increased rhythmicity in hypertensive arterial smooth muscle is linked to transient receptor potential canonical channels. J Cell Mol Med. 2010;14:2483–94.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Jackson WF. Oscillations in active tension in hamster aortas: role of the endothelium. Blood Vessels. 1988;25:144–56.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Mauban JR, Wier WG. Essential role of EDHF in the initiation and maintenance of adrenergic vasomotion in rat mesenteric arteries. Am J Physiol Heart Circ Physiol. 2004;287:H608–16.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Rahman A, Matchkov V, Nilsson H, Aalkjaer C. Effects of cGMP on coordination of vascular smooth muscle cells of rat mesenteric small arteries. J Vasc Res. 2005;42:301–11.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Dirnagl U, Lindauer U, Villringer A. Nitric oxide synthase blockade enhances vasomotion in the cerebral microcirculation of anesthetized rats. Microvasc Res. 1993;45:318–23.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Bertuglia S, Colantuoni A, Intaglietta M. Capillary reperfusion after L-arginine, L-NMMA, and L-NNA treatment in cheek pouch microvasculature. Microvasc Res. 1995;50:162–74.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Jackson WF, Mulsch A, Busse R. Rhythmic smooth muscle activity in hamster aortas is mediated by continuous release of NO from the endothelium. Am J Phys. 1991;260:H248–53.Google Scholar
  78. 78.
    Yamamoto Y, Klemm MF, Edwards FR, Suzuki H. Intercellular electrical communication among smooth muscle and endothelial cells in guinea-pig mesenteric arterioles. J Physiol. 2001;535:181–95.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Jacobsen JC, Aalkjaer C, Matchkov VV, Nilsson H, Freiberg JJ, Holstein-Rathlou NH. Heterogeneity and weak coupling may explain the synchronization characteristics of cells in the arterial wall. Philos Trans A Math Phys Eng Sci. 2008;366:3483–502.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Ledoux J, Taylor MS, Bonev AD, Hannah RM, Solodushko V, Shui B, Tallini Y, Kotlikoff MI, Nelson MT. Functional architecture of inositol 1,4,5-trisphosphate signaling in restricted spaces of myoendothelial projections. Proc Natl Acad Sci U S A. 2008;105:9627–32.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Segal SS. Integration and modulation of intercellular signaling underlying blood flow control. J Vasc Res. 2015;52:136–57.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Zang WJ, Balke CW, Wier WG. Graded α1-adrenoceptor activation of arteries involves recruitment of smooth muscle cells to produce ‘all or none’ Ca2+ signals. Cell Calcium. 2001;29:327–34.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Smith R, Imtiaz M, Banney D, Paul JW, Young RC. Why the heart is like an orchestra and the uterus is like a soccer crowd. Am J Obstet Gynecol. 2015;213:181–5.PubMedCrossRefGoogle Scholar
  84. 84.
    Zhang J, Chen L, Raina H, Blaustein MP, Wier WG. In vivo assessment of artery smooth muscle [Ca2+]i and MLCK activation in FRET-based biosensor mice. Am J Physiol Heart Circ Physiol. 2010;299:H946–56.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Wang Y, Chen L, Wier WG, Zhang J. Intravital Förster resonance energy transfer imaging reveals elevated [Ca2+]i and enhanced sympathetic tone in femoral arteries of angiotensin II-infused hypertensive biosensor mice. J Physiol. 2013;591:5321–36.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Zacharia J, Mauban JR, Raina H, Fisher SA, Wier WG. High vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via alpha1A- and alpha1D-adrenoceptor subtypes. PLoS One. 2013;8:e65969.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Funk W, Endrich B, Messmer K, Intaglietta M. Spontaneous arteriolar vasomotion as a determinant of peripheral vascular resistance. Int J Microcirc Clin Exp. 1983;2:11–25.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Bertuglia S, Colantuoni A, Coppini G, Intaglietta M. Hypoxia- or hyperoxia-induced changes in arteriolar vasomotion in skeletal muscle microcirculation. Am J Phys. 1991;260:H362–72.Google Scholar
  89. 89.
    Tsai AG, Intaglietta M. Evidence of flowmotion induced changes in local tissue oxygenation. Int J Microcirc Clin Exp. 1993;12:75–88.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Parthimos D, Edwards DH, Griffith TM. Comparison of chaotic and sinusoidal vasomotion in the regulation of microvascular flow. Cardiovasc Res. 1996;31:388–99.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Gratton RJ, Gandley RE, McCarthy JF, Michaluk WK, Slinker BK, McLaughlin MK. Contribution of vasomotion to vascular resistance: a comparison of arteries from virgin and pregnant rats. J Appl Physiol. 1998;85:2255–60.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Rücker M, Strobel O, Vollmar B, Roesken F, Menger MD. Vasomotion in critically perfused muscle protects adjacent tissues from capillary perfusion failure. J Physiol Heart Circ Physiol. 2000;279:H550–8.CrossRefGoogle Scholar
  93. 93.
    Meyer C, de Vries G, Davidge ST, Mayes DC. Reassessing the mathematical modeling of the contribution of vasomotion to vascular resistance. J Appl Physiol. 2002;92:888–9.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Thorn CE, Kyte H, Slaff DW, Shore AC. An association between vasomotion and oxygen extraction. Am J Physiol Heart Circ Physiol. 2011;301:H442–9.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Di Marco LY, Farkas E, Martin C, Venneri A, Frangi AF. Is vasomotion in cerebral arteries impaired in Alzheimer’s disease? J Alzheimers Dis. 2015;46:35–53.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Tarantini S, Tran CHT, Gordon GR, Ungvari Z, Csiszar A. Impaired neurovascular coupling in aging and Alzheimer’s disease: contribution of astrocyte dysfunction and endothelial impairment to cognitive decline. Exp Gerontol. 2017;94:52–8.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Iadecola C, Nedergaard M. Glial regulation of the cerebral microvasculature. Nat Neurosci. 2007;10:1369–76.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Lecrux C, Hamel E. The neurovascular unit in brain function and disease. Acta Physiol (Oxford). 2011;203:47–59.CrossRefGoogle Scholar
  99. 99.
    Iadecola C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron. 2017;96:17–42.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Ogawa S, Lee TM, Nayak AS, Glynn P. Oxygenation-sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields. Magn Reson Med. 1990;14:68–78.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Ogawa S, Lee TM, Kay AR, Tank DW. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A. 1990;87:9868–72.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Chen BR, Bouchard MB, McCaslin AF, Burgess SA, Hillman EM. High-speed vascular dynamics of the hemodynamic response. NeuroImage. 2011;54:1021–30.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Nir Y, Hasson U, Levy I, Yeshurun Y, Malach R. Widespread functional connectivity and fMRI fluctuations in human visual cortex in the absence of visual stimulation. NeuroImage. 2006;30:1313–24.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci. 2007;8:700–11.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Bruyns-Haylett M, Harris S, Boorman L, Zheng Y, Berwick J, Jones M. The resting-state neurovascular coupling relationship: rapid changes in spontaneous neural activity in the somatosensory cortex are associated with haemodynamic fluctuations that resemble stimulus-evoked haemodynamics. Eur J Neurosci. 2013;38:2902–16.PubMedPubMedCentralGoogle Scholar
  106. 106.
    Liu TT. Neurovascular factors in resting-state functional MRI. NeuroImage. 2013;80:339–48.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Mayhew JEW, Askew S, Zheng Y, Porrill J, Westby GWM, Redgrave P, Rector DM, Harper RM. Cerebral vasomotion: a 0.1-Hz oscillation in reflected light imaging of neural activity. NeuroImage. 1996;4:183–93.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Obrig H, Neufang M, Wenzel R, Kohl M, Steinbrink J, Einhäupl K, Villringer A. Spontaneous low frequency oscillations of cerebral hemodynamics and metabolism in human adults. NeuroImage. 2000;12:623–39.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Logothetis NK. The neural basis of the blood-oxygen-level-dependent functional magnetic resonance imaging signal. Philos Trans R Soc Lond B. 2002;357:1003–37.CrossRefGoogle Scholar
  110. 110.
    Logothetis NK. The underpinnings of the BOLD functional magnetic resonance imaging signal. J Neurosci. 2003;23:3963–71.PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Logothetis NK. What we can do and what we cannot do with fMRI. Nature. 2008;453:869–78.PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Lauritzen M. Reading vascular changes in brain imaging: is dendritic calcium the key? Nat Rev Neurosci. 2005;6:77–85.PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Devor A, Sakadžić S, Srinivasan VJ, Yaseen MA, Nizar K, Saisan PA, Tian P, Dale AM, Vinogradov SA, Franceschini MA, Boas DA. Frontiers in optical imaging of cerebral blood flow and metabolism. J Cereb Blood Flow Metab. 2012;32:1259–76.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Mishra A, Kurth-Nelson Z, Hall C, Howarth C. Interpreting BOLD: a dialogue between cognitive and cellular neuroscience. Theo Murphy Meeting Themed Issue. Philos Trans R Soc B. 2016;371(1705):20150348–61.CrossRefGoogle Scholar
  115. 115.
    Logothetis NK, Pauls J, Augath M, Trinath T, Oeltermann A. Neurophysiological investigation of the basis of the fMRI signal. Nature. 2001;412:150–7.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Niessing J, Ebisch B, Schmidt KE, Niessing M, Singer W, Galuske RA. Hemodynamic signals correlate tightly with synchronized gamma oscillations. Science. 2005;309:948–51.PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Nir Y, Mukamel R, Dinstein I, Privman E, Harel M, Fisch L, Gelbard-Sagiv H, Kipervasser S, Andelman F, Neufeld MY, Kramer U, Arieli A, Fried I, Malach R. Interhemispheric correlations of slow spontaneous neuronal fluctuations revealed in human sensory cortex. Nat Neurosci. 2008;11:1100–8.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    He BJ, Raichle ME. The fMRI signal, slow cortical potential and consciousness. Trends Cogn Sci. 2009;13:302–9.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Henrie JA, Shapley R. LFP power spectra in V1 cortex: the graded effect of stimulus contrast. J Neurophysiol. 2005;94:479–90.PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    Pesaran B, Pezaris JS, Sahani M, Mitra PP, Andersen RA. Temporal structure in neuronal activity during working memory in macaque parietal cortex. Nat Neurosci. 2002;5:805–11.PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    Bauer EP, Paz R, Paré D. Gamma oscillations coordinate amygdalo-rhinal interactions during learning. J Neurosci. 2007;27:9369–79.PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Longden T, Dabertrand F, Koide M, Gonzales AL, Tykocki NR, Brayden JE, Hill-Eubanks D, Nelson MT. Capillary K+-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow. Nat Neurosci. 2017;20:717–26.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA, O’Farrell FM, Buchan AM, Lauritzen M, Attwell D. Capillary pericytes regulate cerebral blood flow in health and disease. Nature. 2014;508:55–60.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Jackson WF. Boosting the signal: Endothelial inward rectifier K+ channels. Microcirculation. 2017;24:e12319.CrossRefGoogle Scholar
  125. 125.
    Tallini YN, Brekke JF, Shui B, Doran R, Hwang SM, Nakai J, Salama G, Segal SS, Kotlikoff MI. Propagated endothelial Ca2+ waves and arteriolar dilation in vivo: measurements in Cx40BAC–GCaMP2 transgenic mice. Circ Res. 2007;101:1300–9.PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Chen BR, Kozberg MG, Bouchard MB, Shaik MA, Hillman EMC. A critical role of the vascular endothelium in functional neurovascular coupling in the brain. J Am Heart Assoc. 2014;3:e000787.PubMedPubMedCentralGoogle Scholar
  127. 127.
    Sinkler SY, Segal SS. Rapid versus slow ascending vasodilatation: intercellular conduction versus flow-mediated signalling with tetanic versus rhythmic muscle contractions. J Physiol. 2017;595:7149–65.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Bernardi L, Rossi M, Fratino P, Finardi G, Mevio E, Orlandi C. Relationship between phasic changes in human skin blood flow and autonomic tone. Microvasc Res. 1989;37:16–27.PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    Borovik A, Golubinskaya V, Tarasova O, Aalkjaer C, Nilsson H. Phase resetting of arterial vasomotion by burst stimulation of perivascular nerves. J Vasc Res. 2005;42:165–73.PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    Bernardi L, Rossi M, Leuzzi S, Mevio E, Fornasari G, Calciati A, Orlandi C, Fratino P. Reduction of 0.1 Hz microcirculatory fluctuations as evidence of sympathetic dysfunction in insulin-dependent diabetes. Cardiovasc Res. 1997;34:185–91.PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Meyer MF, Rose CJ, Hülsmann JO, Schatz H, Pfohl M. Impaired 0.1-Hz vasomotion assessed by laser Doppler anemometry as an early index of peripheral sympathetic neuropathy in diabetes. Microvasc Res. 2003;65:88–95.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • William C. Cole
    • 1
    Email author
  • Grant R. Gordon
    • 1
  • Andrew P. Braun
    • 1
  1. 1.Department of Physiology and Pharmacology, Libin Cardiovascular Institute, Cumming School of MedicineUniversity of CalgaryCalgaryCanada

Personalised recommendations