Advertisement

Lymphatic Vessel Pumping

  • Pierre-Yves von der WeidEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1124)

Abstract

The lymphatic system extends its network of vessels throughout most of the body. Lymphatic vessels carry a fluid rich in proteins, immune cells, and long-chain fatty acids known as lymph. It results from an excess of interstitial tissue fluid collected from the periphery and transported centrally against hydrostatic pressure and protein concentration gradients. Thus, this one-way transport system is a key component in the maintenance of normal interstitial tissue fluid volume, protein concentration and fat metabolism, as well as the mounting of adequate immune responses as lymph passes through lymph nodes. In most cases, lymph is actively propelled via rhythmical phasic contractions through a succession of valve-bordered chambers constituting the lymphatic vessels. This contraction/relaxation cycle, or lymphatic pumping, is initiated in the smooth muscle cells present in the vessel wall by a pacemaker mechanism generating voltage-gated Ca2+ channel-induced action potentials. The action potentials provide the depolarization and Ca2+ influx essential for the engagement of the contractile machinery leading to the phasic constrictions of the lymphatic chambers and forward movement of lymph. The spontaneous lymphatic constrictions can be observed in isolated vessels in the absence of any external stimulation, while they are critically regulated by physical means, such as lymph-induced transmural pressure and flow rate, as well as diffusible molecules released from the lymphatic endothelium, perivascular nerve varicosities, blood and surrounding tissues/cells. In this chapter, we describe the latest findings which are improving our understanding of the mechanisms underlying spontaneous lymphatic pumping and discuss current theories about their physiological initiation.

Keywords

Lymphatic system Lymphatic vessel Lymphatic pumping Lymphatic muscle cell Lymphatic pacemaker Spontaneous transient depolarization Ca2+-activated Cl channel Intracellular Ca2+ store 

References

  1. 1.
    Schmid-Schonbein GW. Microlymphatics and lymph flow. Physiol Rev. 1990;70(4):987–1028.PubMedCrossRefGoogle Scholar
  2. 2.
    Azzali G, Arcari ML. Ultrastructural and three-dimensional aspects of the lymphatic vessels of the absorbing peripheral lymphatic apparatus in Peyer’s patches of the rabbit. Anat Rec. 2000;258(1):71–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Casley-Smith JR. The role of the endothelial intercellular junctions in the functioning of the initial lymphatics. Angiologica. 1972;9(2):106–31.PubMedGoogle Scholar
  4. 4.
    Baluk P, Fuxe J, Hashizume H, Romano T, Lashnits E, Butz S, et al. Functionally specialized junctions between endothelial cells of lymphatic vessels. J Exp Med. 2007;204(10):2349–62.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Mendoza E, Schmid-Schonbein GW. A model for mechanics of primary lymphatic valves. J Biomech Eng. 2003;125(3):407–14.PubMedCrossRefGoogle Scholar
  6. 6.
    Ryan TJ. Structure and function of lymphatics. J Invest Dermatol. 1989;93(2 Suppl):18S–24S.PubMedCrossRefGoogle Scholar
  7. 7.
    Schmid-Schonbein GW. The second valve system in lymphatics. Lymphat Res Biol. 2003;1(1):25–9; discussion 9–31PubMedCrossRefGoogle Scholar
  8. 8.
    Schulte-Merker S, Sabine A, Petrova TV. Lymphatic vascular morphogenesis in development, physiology, and disease. J Cell Biol. 2011;193(4):607–18.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Leak L, Burke J. Ultrastructural studies on the lymphatic anchoring filaments. J Cell Biol. 1968;36:129–49.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Barrowman JA, Tso P, Kvietys PR, Granger DN. Gastrointestinal lymph and lymphatics. In: Johnston M, editor. Experimental biology of the lymphatic circulation. Amsterdam: Elsevier Science Publishers; 1985.Google Scholar
  11. 11.
    Casley-Smith JR. Electron microscopical observations on the dilated lymphatics in oedematous regions and their collapse following hyaluronidase administration. Br J Exp Pathol. 1967;48:680–6.Google Scholar
  12. 12.
    Yoffey JM, Courtice FC. Lymphatics, lymph and the lymphomyeloid complex. London: Academic Press; 1970.Google Scholar
  13. 13.
    Horstmann E. Uber die funktionelle Struktur der mesenterialen Lymphgefasse. Morphol Jahrb. 1952;91:483–510.Google Scholar
  14. 14.
    Florey HW. Observations on the contractility of lacteals. Part I. J Physiol. 1927;62:267–72.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Aukland K, Reed RK. Interstitial-lymphatic mechanisms in the control of extracellular fluid volume. Physiol Rev. 1993;73(1):1–78.PubMedCrossRefGoogle Scholar
  16. 16.
    Grimaldi A, Moriondo A, Sciacca L, Guidali ML, Tettamanti G, Negrini D. Functional arrangement of rat diaphragmatic initial lymphatic network. Am J Physiol Heart Circ Physiol. 2006;291(2):H876–85.PubMedCrossRefGoogle Scholar
  17. 17.
    Moriondo A, Mukenge S, Negrini D. Transmural pressure in rat initial subpleural lymphatics during spontaneous or mechanical ventilation. Am J Physiol Heart Circ Physiol. 2005;289(1):H263–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Negrini D, Ballard ST, Benoit JN. Contribution of lymphatic myogenic activity and respiratory movements to pleural lymph flow. J Appl Physiol (1985). 1994;76(6):2267–74.CrossRefGoogle Scholar
  19. 19.
    Negrini D, Del Fabbro M. Subatmospheric pressure in the rabbit pleural lymphatic network. J Physiol. 1999;520(Pt 3):761–9.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Negrini D, Moriondo A, Mukenge S. Transmural pressure during cardiogenic oscillations in rodent diaphragmatic lymphatic vessels. Lymphat Res Biol. 2004;2(2):69–81.PubMedCrossRefGoogle Scholar
  21. 21.
    Nicoll PA, Hogan RD. Pressures associated with lymphatic capillary contraction. Microvasc Res. 1978;15(2):257–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Higuchi M, Fokin A, Masters TN, Robicsek F, Schmid-Schonbein GW. Transport of colloidal particles in lymphatics and vasculature after subcutaneous injection. J Appl Physiol (1985). 1999;86(4):1381–7.CrossRefGoogle Scholar
  23. 23.
    Trzewik J, Mallipattu SK, Artmann GM, Delano FA, Schmid-Schonbein GW. Evidence for a second valve system in lymphatics: endothelial microvalves. FASEB J. 2001;15(10):1711–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Farnsworth RH, Achen MG, Stacker SA. The evolving role of lymphatics in cancer metastasis. Curr Opin Immunol. 2018;53:64–73.PubMedCrossRefGoogle Scholar
  25. 25.
    Al-Kofahi M, Becker F, Gavins FN, Woolard MD, Tsunoda I, Wang Y, et al. IL-1beta reduces tonic contraction of mesenteric lymphatic muscle cells, with the involvement of cycloxygenase-2 and prostaglandin E2. Br J Pharmacol. 2015;172(16):4038–51.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Aldrich MB, Sevick-Muraca EM. Cytokines are systemic effectors of lymphatic function in acute inflammation. Cytokine. 2013;64(1):362–9.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Chen Y, Rehal S, Roizes S, Zhu HL, Cole WC, von der Weid PY. The pro-inflammatory cytokine TNF-alpha inhibits lymphatic pumping via activation of the NF-kappaB-iNOS signaling pathway. Microcirculation. 2017;24(3):e12364.CrossRefGoogle Scholar
  28. 28.
    Paniagua D, Jimenez L, Romero C, Vergara I, Calderon A, Benard M, et al. Lymphatic route of transport and pharmacokinetics of Micrurus fulvius (coral snake) venom in sheep. Lymphology. 2012;45(4):144–53.PubMedGoogle Scholar
  29. 29.
    McLennan DN, Porter CJ, Edwards GA, Heatherington AC, Martin SW, Charman SA. The absorption of darbepoetin alfa occurs predominantly via the lymphatics following subcutaneous administration to sheep. Pharm Res. 2006;23(9):2060–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Chikly B. Who discovered the lymphatic system. Lymphology. 1997;30(4):186–93.PubMedGoogle Scholar
  31. 31.
    Tso P, Balint JA. Formation and transport of chylomicrons by enterocytes to the lymphatics. Am J Phys. 1986;250(6 Pt 1):G715–26.Google Scholar
  32. 32.
    Phan CT, Tso P. Intestinal lipid absorption and transport. Front Biosci. 2001;6:D299–319.PubMedCrossRefGoogle Scholar
  33. 33.
    Nordskog BK, Phan CT, Nutting DF, Tso P. An examination of the factors affecting intestinal lymphatic transport of dietary lipids. Adv Drug Deliv Rev. 2001;50(1–2):21–44.PubMedCrossRefGoogle Scholar
  34. 34.
    Tso P, Nauli A, Lo CM. Enterocyte fatty acid uptake and intestinal fatty acid-binding protein. Biochem Soc Trans. 2004;32(Pt 1):75–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Borgstrom B, Laurell CB. Studies of lymph and lymph-proteins during absorption of fat and saline by rats. Acta Physiol Scand. 1953;29(2–3):264–80.PubMedCrossRefGoogle Scholar
  36. 36.
    Simmonds WJ. The effect of fluid, electrolyte and food intake on thoracic duct lymph flow in unanaesthetized rats. Aust J Exp Biol Med Sci. 1954;32(3):285–99.PubMedCrossRefGoogle Scholar
  37. 37.
    Zweifach BW, Prather JW. Micromanipulation of pressure in terminal lymphatics in the mesentery. Am J Phys. 1975;228(5):1326–35.CrossRefGoogle Scholar
  38. 38.
    Davis MJ, Rahbar E, Gashev AA, Zawieja DC, Moore JE Jr. Determinants of valve gating in collecting lymphatic vessels from rat mesentery. Am J Physiol Heart Circ Physiol. 2011;301(1):H48–60.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Chakraborty S, Davis MJ, Muthuchamy M. Emerging trends in the pathophysiology of lymphatic contractile function. Semin Cell Dev Biol. 2015;38:55–66.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Somlyo AP, Somlyo AV. Signal transduction and regulation in smooth muscle. Nature. 1994;372(6503):231–6.CrossRefGoogle Scholar
  41. 41.
    Pfitzer G. Invited review: regulation of myosin phosphorylation in smooth muscle. J Appl Physiol. 2001;91(1):497–503.PubMedCrossRefGoogle Scholar
  42. 42.
    Muthuchamy M, Gashev A, Boswell N, Dawson N, Zawieja D. Molecular and functional analyses of the contractile apparatus in lymphatic muscle. FASEB J. 2003;17(8):920–2.PubMedCrossRefGoogle Scholar
  43. 43.
    von der Weid PY, Muthuchamy M. Regulatory mechanisms in lymphatic vessel contraction under normal and inflammatory conditions. Pathophysiology. 2010;17(4):263–76.PubMedCrossRefGoogle Scholar
  44. 44.
    McHale NG, Roddie IC, Thornbury KD. Nervous modulation of spontaneous contractions in bovine mesenteric lymphatics. J Physiol Lond. 1980;309(461):461–72.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Hanley CA, Elias RM, Johnston MG. Is endothelium necessary for transmural pressure-induced contractions of bovine truncal lymphatics? Microvasc Res. 1992;43(2):134–46.PubMedCrossRefGoogle Scholar
  46. 46.
    Allen JM, McHale NG, Rooney BM. Effect of norepinephrine on contractility of isolated mesenteric lymphatics. Am J Phys. 1983;244(4):H479–86.Google Scholar
  47. 47.
    Azuma T, Ohhashi T, Sakaguchi M. Electrical activity of lymphatic smooth muscles. Proc Soc Exp Biol Med. 1977;155(2):270–3.PubMedCrossRefGoogle Scholar
  48. 48.
    Kirkpatrick CT, McHale NG. Electrical and mechanical activity of isolated lymphatic vessels [proceedings]. J Physiol. 1977;272(1):33P–4P.PubMedGoogle Scholar
  49. 49.
    Mislin H. Die motorik Lymphgefässe und der Regulation der Lymphherzen. Handbuch der Algemeinen Pathologie. 3/6. Berlin: Springer-Verlag; 1973. p. 219–38.Google Scholar
  50. 50.
    Mislin H. The lymphangion. In: Foldi M, Casley-Smith R, editors. Lymphangiology. Stuttgart: Schattauer-Verlag; 1983. p. 165–75.Google Scholar
  51. 51.
    Orlov RS, Borigora RP, Mundriko ES. Investigation of contractile and electrical activity of smooth muscle of lymphatic vessels. In: Bulbring EaS MF, editor. Physiology of smooth muscle. New York: Ranon; 1976. p. 147–52.Google Scholar
  52. 52.
    Chan AK, Vergnolle N, Hollenberg MD, von der Weid P-Y. Proteinase-activated receptor 2 modulates guinea-pig mesenteric lymphatic vessel pacemaker potential and contractile activity. J Physiol. 2004;560:563–76.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    van Helden DF. Pacemaker potentials in lymphatic smooth muscle of the guinea-pig mesentery. J Physiol. 1993;471:465–79.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    von der Weid PY, van Helden DF. Beta-adrenoceptor-mediated hyperpolarization in lymphatic smooth muscle of guinea pig mesentery. Am J Phys. 1996;270(5 Pt 2):H1687–95.Google Scholar
  55. 55.
    von der Weid PY, Lee S, Imtiaz MS, Zawieja DC, Davis MJ. Electrophysiological properties of rat mesenteric lymphatic vessels and their regulation by stretch. Lymphat Res Biol. 2014;12(2):66–75.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Hugues GA, Harper AA. The effect of Na+-K+-2Cl− cotransport inhibition and chloride channel blockers on membrane potential and contractility in rat lymphatic smooth muscle in vitro. J Physiol. 1999;518P:127P.Google Scholar
  57. 57.
    Ohhashi T, Azuma T. Effect of potassium on membrane potential and tension development in bovine mesenteric lymphatics. Microvasc Res. 1982;23(1):93–8.PubMedCrossRefGoogle Scholar
  58. 58.
    Ohhashi T, Azuma T, Sakaguchi M. Transmembrane potentials in bovine lymphatic smooth muscle. Proc Soc Exp Biol Med. 1978;159:350–2.PubMedCrossRefGoogle Scholar
  59. 59.
    Ward SM, McHale NG, Sanders KM. A method for recording transmembrane potentials in bovine mesenteric lymphatics. Ir J Med Sci. 1989;158:129 (abstract).Google Scholar
  60. 60.
    Telinius N, Mohanakumar S, Majgaard J, Kim S, Pilegaard H, Pahle E, et al. Human lymphatic vessel contractile activity is inhibited in vitro but not in vivo by the calcium channel blocker nifedipine. J Physiol. 2014;592(21):4697–714.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Zawieja SD, Castorena-Gonzalez JA, Scallan J, Davis MJ. Differences in L-type calcium channel activity partially underlie the regional dichotomy in pumping behavior by murine peripheral and visceral lymphatic vessels. Am J Physiol Heart Circ Physiol. 2018;314:H991–H1010.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Scallan JP, Zawieja SD, Castorena-Gonzalez JA, Davis MJ. Lymphatic pumping: mechanics, mechanisms and malfunction. J Physiol. 2016;594:5749–68.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Allen JM, McHale NG. The effect of known K+-channel blockers on the electrical activity of bovine lymphatic smooth muscle. Pflugers Arch. 1988;411(2):167–72.PubMedCrossRefGoogle Scholar
  64. 64.
    Cotton KD, Hollywood MA, McHale NG, Thornbury KD. Outward currents in smooth muscle cells isolated from sheep mesenteric lymphatics. J Physiol Lond. 1997;503:1–11.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Cotton KD, Hollywood MA, McHale NG, Thornbury KD. Ca2+ current and Ca(2+)-activated chloride current in isolated smooth muscle cells of the sheep urethra. J Physiol Lond. 1997;505:121–31.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Toland HM, McCloskey KD, Thornbury KD, McHale NG, Hollywood MA. Ca(2+)-activated Cl(−) current in sheep lymphatic smooth muscle. Am J Phys Cell Physiol. 2000;279(5):C1327–35.CrossRefGoogle Scholar
  67. 67.
    von der Weid P-Y. ATP-sensitive K+ channels in smooth muscle cells of guinea-pig mesenteric lymphatics: role in nitric oxide and beta-adrenoceptor agonist-induced hyperpolarizations. Br J Pharmacol. 1998;125(1):17–22.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Telinius N, Kim S, Pilegaard H, Pahle E, Nielsen J, Hjortdal V, et al. The contribution of K(+) channels to human thoracic duct contractility. Am J Physiol Heart Circ Physiol. 2014;307(1):H33–43.PubMedCrossRefGoogle Scholar
  69. 69.
    von der Weid P-Y, Rahman M, Imtiaz MS, van Helden DF. Spontaneous transient depolarizations in lymphatic vessels of the guinea pig mesentery: pharmacology and implication for spontaneous contractility. Am J Physiol Heart Circ Physiol. 2008;295(5):H1989–2000.PubMedCrossRefGoogle Scholar
  70. 70.
    Ward SM, Sanders KM, Thornbury KD, McHale NG. Spontaneous electrical activity in isolated bovine lymphatics recorded by intracellular microelectrodes. J Physiol. 1991;438:168P.Google Scholar
  71. 71.
    Beckett EA, Hollywood MA, Thornbury KD, McHale NG. Spontaneous electrical activity in sheep mesenteric lymphatics. Lymphat Res Biol. 2007;5(1):29–43.PubMedCrossRefGoogle Scholar
  72. 72.
    Telinius N, Majgaard J, Kim S, Katballe N, Pahle E, Nielsen J, et al. Voltage-gated sodium channels contribute to action potentials and spontaneous contractility in isolated human lymphatic vessels. J Physiol. 2015;593(14):3109–22.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    van Helden DF, von der Weid P-Y, Crowe MJ. Electrophysiology of lymphatic smooth muscle. In: Bert J, Laine GA, McHale NG, Reed R, Winlove P, editors. Interstitium, connective tissue, and lymphatics. London: Portland Press; 1995. p. 221–36.Google Scholar
  74. 74.
    Atchison DJ, Johnston MG. Role of extra- and intracellular Ca2+ in the lymphatic myogenic response. Am J Phys. 1997;272:R326–R33.Google Scholar
  75. 75.
    McHale NG, Allen JM, Iggulden HL. Mechanism of alpha-adrenergic excitation in bovine lymphatic smooth muscle. Am J Phys. 1987;252(5 Pt 2):H873–8.Google Scholar
  76. 76.
    Hollywood MA, Cotton KD, Thorbury KD, McHale NG. Isolated sheep mesenteric lymphatic smooth muscle possess both T- and L-type calcium currents. J Physiol. 1997;501P:P109–10.Google Scholar
  77. 77.
    Lee S, Roizes S, von der Weid PY. Distinct roles of L- and T-type voltage-dependent Ca2+ channels in regulation of lymphatic vessel contractile activity. J Physiol. 2014;592(Pt 24):5409–27.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Hollywood MA, Cotton KD, Thorbury KD, McHale NG. Tetrodotoxin-sensitive sodium current in sheep lymphatic smooth muscle. J Physiol. 1997;503:13–20.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    McCloskey KD, Toland HM, Hollywood MA, Thorbury KD, McHale NG. Hyperpolarization-activated inward current in isolated sheep mesenteric lymphatic smooth muscle. J Physiol. 1999;521:201–11.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Negrini D, Marcozzi C, Solari E, Bossi E, Cinquetti R, Reguzzoni M, et al. Hyperpolarization-activated cyclic nucleotide-gated channels in peripheral diaphragmatic lymphatics. Am J Physiol Heart Circ Physiol. 2016;311(4):H892–903.PubMedCrossRefGoogle Scholar
  81. 81.
    Fox JL, von der Weid PY. Effects of histamine on the contractile and electrical activity in isolated lymphatic vessels of the guinea-pig mesentery. Br J Pharmacol. 2002;136(8):1210–8.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    van Helden DF, von der Weid P-Y, Crowe MJ. Intracellular Ca2+ release: a basis for electrical pacemaking in lymphatic smooth muscle. In: Tomita T, Bolton TB, editors. Smooth muscle excitation. London: Academic Press; 1996. p. 355–73.Google Scholar
  83. 83.
    von der Weid P-Y, Zhao J, van Helden DF. Nitric oxide decreases pacemaker activity in lymphatic vessels of guinea pig mesentery. Am J Phys. 2001;280(6):H2707–16.Google Scholar
  84. 84.
    Imtiaz MS, Zhao J, Hosaka K, von der Weid PY, Crowe M, van Helden DF. Pacemaking through Ca2+ stores interacting as coupled oscillators via membrane depolarization. Biophys J. 2007;92(11):3843–61.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Lamb FS, Barna TJ. Chloride ion currents contribute functionally to norepinephrine-induced vascular contraction. Am J Phys. 1998;275:H151–60.Google Scholar
  86. 86.
    Yuan XJ. Role of calcium-activated chloride current in regulating pulmonary vasomotor tone. Am J Phys. 1997;272:L959–68.Google Scholar
  87. 87.
    Gui P, Zawieja SD, Li M, Bulley S, Jaggar JH, Rock JR, et al. The Ca2+-activated Cl- Channel TMEM16A(ANO1) modulates, but is not required for, pacemaking in mouse lymphatic vessels. FASEB J. 2016;30:726.3.Google Scholar
  88. 88.
    McHale NG, Roddie IC. The effect of transmural pressure on pumping activity in isolated bovine lymphatic vessels. J Physiol Lond. 1976;261(2):255–69.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Benoit JN, Zawieja DC, Goodman AH, Granger HJ. Characterization of intact mesenteric lymphatic pump and its responsiveness to acute edemagenic stress. Am J Phys. 1989;257:H2059–69.Google Scholar
  90. 90.
    van Helden DF. Spontaneous and noradrenaline-induced transient depolarizations in the smooth muscle of guinea-pig mesenteric vein. J Physiol. 1991;437(511):511–41.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Munn LL. Mechanobiology of lymphatic contractions. Semin Cell Dev Biol. 2015;38:67–74.PubMedCrossRefGoogle Scholar
  92. 92.
    Ferrusi I, Zhao J, van Helden DF, von der Weid P-Y. Cyclopiazonic acid decreases spontaneous transient depolarizations in guinea pig mesenteric lymphatic vessels in endothelium-dependent and -independent manners. Am J Phys. 2004;286(6):H2287–95.Google Scholar
  93. 93.
    Atchison DJ, Rodela H, Johnston MG. Intracellular calcium stores modulation in lymph vessels depends on wall stretch. Can J Physiol Pharmacol. 1998;76(4):367–72.PubMedCrossRefGoogle Scholar
  94. 94.
    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(2):278–85.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Crowe MJ, von der Weid PY, Brock JA, Van Helden DF. Co-ordination of contractile activity in guinea-pig mesenteric lymphatics. J Physiol. 1997;500(Pt 1):235–44.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Zawieja DC, Davis KL, Schuster R, Hinds WM, Granger HJ. Distribution, propagation, and coordination of contractile activity in lymphatics. Am J Physiol Heart Circ Physiol. 1993;264(4 Pt 2):H1283–H91.CrossRefGoogle Scholar
  97. 97.
    McHale NG, Meharg MK. Co-ordination of pumping in isolated bovine lymphatic vessels. J Physiol. 1992;450:503–12.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Hirano Y, Fozzard HA, January CT. Characteristics of L- and T-type Ca2+ currents in canine cardiac Purkinje cells. Am J Phys. 1989;256(5 Pt 2):H1478–92.Google Scholar
  99. 99.
    Bradley JE, Anderson UA, Woolsey SM, Thornbury KD, McHale NG, Hollywood MA. Characterization of T-type calcium current and its contribution to electrical activity in rabbit urethra. Am J Phys Cell Physiol. 2004;286(5):C1078–88.CrossRefGoogle Scholar
  100. 100.
    Yanai Y, Hashitani H, Kubota Y, Sasaki S, Kohri K, Suzuki H. The role of Ni(2+)-sensitive T-type Ca(2+) channels in the regulation of spontaneous excitation in detrusor smooth muscles of the guinea-pig bladder. BJU Int. 2006;97(1):182–9.PubMedCrossRefGoogle Scholar
  101. 101.
    Huser J, Blatter LA, Lipsius SL. Intracellular Ca2+ release contributes to automaticity in cat atrial pacemaker cells. J Physiol. 2000;524(Pt 2):415–22.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Zhou Z, Lipsius SL. T-type calcium current in latent pacemaker cells isolated from cat right atrium. J Mol Cell Cardiol. 1994;26(9):1211–9.PubMedCrossRefGoogle Scholar
  103. 103.
    Fleig A, Penner R. The TRPM ion channel subfamily: molecular, biophysical and functional features. Trends Pharmacol Sci. 2004;25(12):633–9.PubMedCrossRefGoogle Scholar
  104. 104.
    Harteneck C. Function and pharmacology of TRPM cation channels. Naunyn Schmiedeberg’s Arch Pharmacol. 2005;371(4):307–14.CrossRefGoogle Scholar
  105. 105.
    Nilius B, Mahieu F, Prenen J, Janssens A, Owsianik G, Vennekens R, et al. The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5-biphosphate. EMBO J. 2006;25(3):467–78.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Kim BJ, Lim HH, Yang DK, Jun JY, Chang IY, Park CS, et al. Melastatin-type transient receptor potential channel 7 is required for intestinal pacemaking activity. Gastroenterology. 2005;129(5):1504–17.PubMedCrossRefGoogle Scholar
  107. 107.
    Kim BJ, So I, Kim KW. The relationship of TRP channels to the pacemaker activity of interstitial cells of Cajal in the gastrointestinal tract. J Smooth Muscle Res. 2006;42(1):1–7.PubMedCrossRefGoogle Scholar
  108. 108.
    Sah R, Mesirca P, Van den Boogert M, Rosen J, Mably J, Mangoni ME, et al. Ion channel-kinase TRPM7 is required for maintaining cardiac automaticity. Proc Natl Acad Sci U S A. 2013;110(32):E3037–46.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Shi J, Mori E, Mori Y, Mori M, Li J, Ito Y, et al. Multiple regulation by calcium of murine homologues of transient receptor potential proteins TRPC6 and TRPC7 expressed in HEK293 cells. J Physiol. 2004;561(Pt 2):415–32.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Welsh DG, Morielli AD, Nelson MT, Brayden JE. Transient receptor potential channels regulate myogenic tone of resistance arteries. Circ Res. 2002;90(3):248–50.PubMedCrossRefGoogle Scholar
  111. 111.
    Launay P, Fleig A, Perraud AL, Scharenberg AM, Penner R, Kinet JP. TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Cell. 2002;109(3):397–407.PubMedCrossRefGoogle Scholar
  112. 112.
    Bridenbaugh EA, Wang W, von der Weid P-Y, Zawieja DC. Detection of TRPV channel expression in rat lymphatic vessels. In: Andrade M, editor. Progress in lymphology XX. Salvador: Icone; 2005. p. 234–5.Google Scholar
  113. 113.
    Harwood CA, Mortimer PS. Causes and clinical manifestations of lymphatic failure. Clin Dermatol. 1995;13(5):459–71.PubMedCrossRefGoogle Scholar
  114. 114.
    Rockson SG. Lymphedema. Am J Med. 2001;110(4):288–95.PubMedCrossRefGoogle Scholar
  115. 115.
    Szuba A, Rockson SG. Lymphedema: classification, diagnosis and therapy. Vasc Med. 1998;3(2):145–56.PubMedCrossRefGoogle Scholar
  116. 116.
    Browse NL, Stewart G. Lymphoedema: pathophysiology and classification. J Cardiovasc Surg. 1985;26(2):91–106.Google Scholar
  117. 117.
    Olszewski WL. Continuing discovery of the lymphatic system in the twenty-first century: a brief overview of the past. Lymphology. 2002;35(3):99–104.PubMedGoogle Scholar
  118. 118.
    Piller NB. Lymphoedema, macrophages and benzopyrones. Lymphology. 1980;13(3):109–19.PubMedGoogle Scholar
  119. 119.
    Kriederman BM, Myloyde TL, Witte MH, Dagenais SL, Witte CL, Rennels M, et al. FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndrome. Hum Mol Genet. 2003;12(10):1179–85.PubMedCrossRefGoogle Scholar
  120. 120.
    Petrova TV, Karpanen T, Norrmen C, Mellor R, Tamakoshi T, Finegold D, et al. Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis. Nat Med. 2004;10(9):974–81.PubMedCrossRefGoogle Scholar
  121. 121.
    Ferrell RE, Levinson KL, Esman JH, Kimak MA, Lawrence EC, Barmada MM, et al. Hereditary lymphedema: evidence for linkage and genetic heterogeneity. Hum Mol Genet. 1998;7(13):2073–8.PubMedCrossRefGoogle Scholar
  122. 122.
    Irrthum A, Karkkainen MJ, Devriendt K, Alitalo K, Vikkula M. Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase. Am J Hum Genet. 2000;67(2):295–301.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Segerstrom K, Bjerle P, Graffman S, Nystrom A. Factors that influence the incidence of brachial oedema after treatment of breast cancer. Scand J Plast Reconstr Surg Hand Surg. 1992;26(2):223–7.PubMedCrossRefGoogle Scholar
  124. 124.
    Modi S, Stanton AW, Svensson WE, Peters AM, Mortimer PS, Levick JR. Human lymphatic pumping measured in healthy and lymphoedematous arms by lymphatic congestion lymphoscintigraphy. J Physiol. 2007;583(Pt 1):271–85.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Taylor MJ. A new insight into the pathogenesis of filarial disease. Curr Mol Med. 2002;2(3):299–302.PubMedCrossRefGoogle Scholar
  126. 126.
    Taylor MJ, Hoerauf A. Wolbachia bacteria of filarial nematodes. Parasitol Today. 1999;15(11):437–42.PubMedCrossRefGoogle Scholar
  127. 127.
    Taylor MJ, Hoerauf A. A new approach to the treatment of filariasis. Curr Opin Infect Dis. 2001;14(6):727–31.PubMedCrossRefGoogle Scholar
  128. 128.
    Taylor MJ, Cross HF, Bilo K. Inflammatory responses induced by the filarial nematode Brugia malayi are mediated by lipopolysaccharide-like activity from endosymbiotic Wolbachia bacteria. J Exp Med. 2000;191(8):1429–36.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Pfarr KM, Debrah AY, Specht S, Hoerauf A. Filariasis and lymphoedema. Parasite Immunol. 2009;31(11):664–72.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Kaiser L, Mupanomunda M, Williams JF. Brugia pahangi-induced contractility of bovine mesenteric lymphatics studied in vitro: a role for filarial factors in the development of lymphedema? Am J Trop Med Hyg. 1996;54(4):386–90.PubMedCrossRefGoogle Scholar
  131. 131.
    Chakraborty S, Gurusamy M, Zawieja DC, Muthuchamy M. Lymphatic filariasis: perspectives on lymphatic remodeling and contractile dysfunction in filarial disease pathogenesis. Microcirculation. 2013;20(5):349–64.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    von der Weid PY. Review article: lymphatic vessel pumping and inflammation—the role of spontaneous constrictions and underlying electrical pacemaker potentials. Aliment Pharmacol Ther. 2001;15(8):1115–29.PubMedCrossRefGoogle Scholar
  133. 133.
    Davis MJ, Lane MM, Davis AM, Durtschi D, Zawieja DC, Muthuchamy M, et al. Modulation of lymphatic muscle contractility by the neuropeptide substance P. Am J Physiol Heart Circ Physiol. 2008;295(2):H587–97.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Hosaka K, Rayner SE, von der Weid PY, Zhao J, Imtiaz MS, van Helden DF. Calcitonin gene-related peptide activates different signaling pathways in mesenteric lymphatics of guinea pigs. Am J Physiol Heart Circ Physiol. 2006;290(2):H813–22.PubMedCrossRefGoogle Scholar
  135. 135.
    Rayner SE, van Helden DF. Evidence that the substance P-induced enhancement of pacemaking in lymphatics of the guinea-pig mesentery occurs through endothelial release of thromboxane A2. Br J Pharmacol. 1997;121(8):1589–96.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    von der Weid PY, Rehal S, Dyrda P, Lee S, Mathias R, Rahman M, et al. Mechanisms of VIP-induced inhibition of the lymphatic vessel pump. J Physiol. 2012;590(Pt 11):2677–91.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Ferguson MK, DeFilippi VJ, Reeder LB. Characterization of contractile properties of porcine mesenteric and tracheobronchial lymphatic smooth muscle. Lymphology. 1994;27(2):71–81.PubMedGoogle Scholar
  138. 138.
    Gashev AA, Davis MJ, Zawieja DC. Inhibition of the active lymph pump by flow in rat mesenteric lymphatics and thoracic duct. J Physiol. 2002;540(Pt 3):1023–37.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Gasheva OY, Zawieja DC, Gashev AA. Contraction-initiated NO-dependent lymphatic relaxation: a self-regulatory mechanism in rat thoracic duct. J Physiol. 2006;575(Pt 3):821–32.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Mizuno R, Koller A, Kaley G. Regulation of the vasomotor activity of lymph microvessels by nitric oxide and prostaglandins. Am J Phys. 1998;274(3 Pt 2):R790–6.Google Scholar
  141. 141.
    Rehal S, Blanckaert P, Roizes S, von der Weid PY. Characterization of biosynthesis and modes of action of prostaglandin E2 and prostacyclin in guinea pig mesenteric lymphatic vessels. Br J Pharmacol. 2009;158(8):1961–70.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Elias RM, Johnston MG. Modulation of fluid pumping in isolated bovine mesenteric lymphatics by a thromboxane/endoperoxide analogue. Prostaglandins. 1988;36(1):97–106.PubMedCrossRefGoogle Scholar
  143. 143.
    Johnston MG, Kanalec A, Gordon JL. Effects of arachidonic acid and its cyclo-oxygenase and lipoxygenase products on lymphatic vessel contractility in vitro. Prostaglandins. 1983;25(1):85–98.PubMedCrossRefGoogle Scholar
  144. 144.
    Johnston MG, Gordon JL. Regulation of lymphatic contractility by arachidonate metabolites. Nature. 1981;293(5830):294–7.PubMedCrossRefGoogle Scholar
  145. 145.
    Johnston MG, Feuer C. Suppression of lymphatic vessel contractility with inhibitors of arachidonic acid metabolism. J Pharmacol Exp Ther. 1983;226(2):603–7.PubMedGoogle Scholar
  146. 146.
    Plaku KJ, von der Weid PY. Mast cell degranulation alters lymphatic contractile activity through action of histamine. Microcirculation. 2006;13(3):219–27.PubMedCrossRefGoogle Scholar
  147. 147.
    Mathias R, von der Weid PY. Involvement of the NO-cGMP-KATP channel pathway in the mesenteric lymphatic pump dysfunction observed in the guinea pig model of TNBS-induced ileitis. Am J Physiol Gastrointest Liver Physiol. 2013;304:G623–34.PubMedCrossRefGoogle Scholar
  148. 148.
    Wu TF, Carati CJ, Macnaughton WK, von der Weid PY. Contractile activity of lymphatic vessels is altered in the TNBS model of guinea pig ileitis. Am J Physiol Gastrointest Liver Physiol. 2006;291(4):G566–74.PubMedCrossRefGoogle Scholar
  149. 149.
    Liao S, Cheng G, Conner DA, Huang Y, Kucherlapati RS, Munn LL, et al. Impaired lymphatic contraction associated with immunosuppression. Proc Natl Acad Sci U S A. 2011;108(46):18784–9.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Gashev AA. Physiologic aspects of lymphatic contractile function: current perspectives. Ann N Y Acad Sci. 2002;979:178–87; discussion 88–96.PubMedCrossRefGoogle Scholar
  151. 151.
    Hanley CA, Elias RM, Movat HZ, Johnston MG. Suppression of fluid pumping in isolated bovine mesenteric lymphatics by interleukin-1: interaction with prostaglandin E2. Microvasc Res. 1989;37(2):218–29.PubMedCrossRefGoogle Scholar
  152. 152.
    Zawieja SD, Wang W, Wu X, Nepiyushchikh ZV, Zawieja DC, Muthuchamy M. Impairments in the intrinsic contractility of mesenteric collecting lymphatics in a rat model of metabolic syndrome. Am J Physiol Heart Circ Physiol. 2012;302(3):H643–53.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Physiology and Pharmacology, Inflammation Research Network and Smooth Muscle Research Group, Snyder Institute for Chronic Diseases, Cumming School of MedicineUniversity of CalgaryCalgaryCanada

Personalised recommendations