Sports Medicine

, Volume 22, Issue 4, pp 228–250 | Cite as

Endothelium-Mediated Control of the Coronary Circulation

Exercise Training-Induced Vascular Adaptations
  • M. H. Laughlin
  • R. M. McAllister
  • J. L. Jasperse
  • S. E. Crader
  • D. A. Williams
  • V. H. Huxley
Review Article


This review discusses the role of the endothelium in the regulation of coronary vascular function. The role of endothelium-mediated mechanisms at rest, during exercise, in exercise training-induced adaptations of coronary function and in the presence of coronary heart disease (CHD) are examined. Mechanisms of control of coronary blood flow are briefly discussed with emphasis on endothelium-mediated control of vascular resistance. The concept that the relative importance of vascular control mechanisms differs as a function of position along the coronary arterial tree is developed and discussed.

Metabolic, myogenic and endothelium-mediated control systems contribute in parallel to regulating coronary blood flow. The relative importance of these mechanisms varies throughout the coronary arterial tree. Endothelium-dependent vasodilation contributes to maintenance of resting coronary blood flow but the endothelium’s role in dilation of small resistance arteries, thereby increasing coronary blood flow during exercise, remains in question. In contrast, the endothelium plays an essential role in dilatation of the conduit coronary arteries during exercise. Atherosclerosis and CHD convert this exercise-induced dilation to a vasoconstriction, apparently due to endothelium dysfunction.

Long term increases in physical activity and exercise training alter the control of coronary blood flow. Adaptations in endothelium-mediated control play a role in these changes. However, the effects of the mode, frequency, and intensity of exercise training bouts and duration of training on adaptive changes in endothelial function have not been established. The role of the endothelium in control of the permeability characteristics of the exchange vessels in the coronary circulation is discussed. Current evidence indicates that vascular permeability is a dynamic characteristic of the vessel wall that is controlled, at least in part, by endothelium-dependent phenomena. Also, preliminary results indicate that exercise training alters microvessel permeability and the control of permeability in the coronary circulation. Further research is needed to provide clarification of the effects of exercise training on coronary endothelial control of vascular resistance and vascular permeability in atherosclerosis and CHD.


Exercise Training Coronary Blood Flow Coronary Circulation Resistance Artery Coronary Vascular Resistance 
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.


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  1. 1.
    Renkin, EM. Blood flow and transcapillary exchange in skeletal and cardiac muscle. In: International Symposium on Coronary Circulation and Energetics of the Myocardium. New York: Karger, 1967: 18–30Google Scholar
  2. 2.
    Laughlin MH, McAllister RM. Exercise training-induced coronary vascular adaptation. J Appl Physiol 1992; 73: 2209–25PubMedGoogle Scholar
  3. 3.
    Renkin EM. Control of microcirculation and exchange. Handbook of Physiology. Bethesda (MD): American Physiological Society, 1984: 627–87Google Scholar
  4. 4.
    Nelson RR, Gobel FL, Jorgensen CR, et al. Hemodynamic predictors of myocardial oxygen consumption during static and dynamic exercise. Circulation 1974; 50: 1179–89PubMedGoogle Scholar
  5. 5.
    Binak K, Harmanci N, Sirmaci N, et al. Oxygen extraction rate of the myocardium at rest and on exercise in various conditions. Br Heart J 1967; 29: 422PubMedGoogle Scholar
  6. 6.
    Jorgensen CR, Gobel FL, Taylor HL, et al. Myocardial blood flow and oxygen consumption during exercise. J Ann NY Acad Sci 1977; 301: 213–23Google Scholar
  7. 7.
    Khouri EM, Gregg DE, Rayford CR. Effect of exercise on cardiac output, left coronary flow and myocardial metabolism in the unanesthetized dog. Circ Res 1965; 17: 427–37PubMedGoogle Scholar
  8. 8.
    Kitamura K, Jorgensen CR, Gobel FL, et al. Hemodynamic correlates of myocardial oxygen consumption during upright exercise. J Applied Physiol 1972; 32: 516–22Google Scholar
  9. 9.
    Lombardo TA, Rose L, Taeschler M, et al. The effect of exercise on coronary blood flow, myocardial oxygen consumption and cardiac efficiency in man. Circulation 1953; 7: 71–8PubMedGoogle Scholar
  10. 10.
    Messer JV, Wagman RJ, Levine HJ, et al. Patterns of human myocardial oxygen extraction during rest and exercise. J Clin Invest 1962; 41: 725–42PubMedGoogle Scholar
  11. 11.
    Rowell LB. Human cardiovascular control. New York: Oxford University Press, 1993: 1–483Google Scholar
  12. 12.
    Laughlin MH, Overholser KA, Bhatte M. Exercise training increases coronary transport reserve in miniature swine. J Appl Physiol 1989; 67: 1140–9PubMedGoogle Scholar
  13. 13.
    Huxley VH, McKay MK, Meyer DJ, et al. Vasoactive hormones and autocrine activation of capillary exchange barrier function. Blood Cells 1993; 19: 309–24PubMedGoogle Scholar
  14. 14.
    Huxley VH, Williams DA. The microcirculation: flow and transport. In: Callow AD, Ernst CB, editors. Vascular surgery: theory and practice. Stamford: Appleton and Lane, 1995: 49–78Google Scholar
  15. 15.
    Jones CJH, Kuo L, Davis MJ, et al. Regulation of coronary blood flow: coordination of heterogeneous control mechanisms in vascular microdomains. Cardiovasc Res 1995: 585-96Google Scholar
  16. 16.
    Feiql EO. Coronary physiology. Physiol Rev 1983: 63: 1–205Google Scholar
  17. 17.
    Shen, W, Ochoa M, Xu X, et al. Role of EDRF/NO in parasympathetic coronary vasodilation following carotid chemoreflex activation in conscious dogs. Am J Physiol 1994; 267: H6O5–13Google Scholar
  18. 18.
    Broten TP, Miyashiro JK, Moncada S, et al. Role of endothelium-derived relaxing factor in parasympathetic coronary vasodilation. Am J Physiol 1992; 262: H1579–84PubMedGoogle Scholar
  19. 19.
    Jones CJH, DeFily DV, Patterson JL, et al. Endothelium-dependent relaxation competes with α1- and α2-adrenergic constriction in the canine epicardial coronary microcirculation. Circulation 1993; 87: 1264–74PubMedGoogle Scholar
  20. 20.
    Duling BR. Control of striated muscle blood flow. In: Crystal RG, West JB, editors. The lung: scientific foundations. New York: Raven Press, 1991: 1497–505Google Scholar
  21. 21.
    Sparks HV. Effect of local metabolic factors on vascular smooth muscle. Handbook of physiology. Bethesda (MD): American Physiological Society, 1980Google Scholar
  22. 22.
    Bayliss WM. On the local reaction of the arterial wall to changes of internal pressure. J Physiol (Lond) 1902; 28: 220–31Google Scholar
  23. 23.
    Johnson PC. The myogenic response. Handbook of physiology: the cardiovascular system. Vol. II. Vascular smooth muscle. Bethesda (MD): American Physiological Society, 1980: 409–42Google Scholar
  24. 24.
    Jones CJH, Kuo L, Davis MJ, et al. Myogenic and flow-dependent control mechanisms in the coronary microcirculation. Basic Res Cardiol 1993; 88: 2–10PubMedGoogle Scholar
  25. 25.
    Kuo L, Davis MJ, Chilian WM. Longitudinal gradients for endothelium-dependent, and -independent vascular responses in the coronary microcirculation. Circulation 1995; 92: 518–25PubMedGoogle Scholar
  26. 26.
    Kuo L, Chilian WM, Davis MJ. Myogenic activity in isolated subepicardial and subendocardial coronary arterioles. Am J Physiol 1989; 255: H1558–62Google Scholar
  27. 27.
    McHale PA, Dube DP, Greenfield JC. Evidence for myogenic vasomotor activity in the coronary circulation. Prog Cardio-vasc Dis 1987; 30: 139–46Google Scholar
  28. 28.
    Schwartz GG, McHale PA, Greenfield JC. Hyperaemic response of the coronary circulation to brief diastolic occlusion in the conscious dog. Circ Res 1989; 50: 28–37Google Scholar
  29. 29.
    Eikens E, Wilckens DEL. Reactive hyperemia in the dog heart: effects of temporarily restricting arterial inflow and of coronary occlusion lasting one and two cardiac cycles. Circ Res 1974; 35: 702–12PubMedGoogle Scholar
  30. 30.
    Daniel TO, Ives HE. Endothelial control of vascular function. News Physiol Sci 1989 4: 139–42Google Scholar
  31. 31.
    Dzau VJ, Gibbons GH. The emerging concept of vascular remodeling. N Engl J Med 1994; 330: 1431–8PubMedGoogle Scholar
  32. 32.
    Dzau VJ, Gibbons GH. The role of the endothelium in vascular remodeling. Cardiovascular significance of endothelium-derived vasoactive factors. Mount Kisco (NY): Futura Publishing Co. Inc., 1991: 281–91Google Scholar
  33. 33.
    Furchgott RF, Vanhoutte PM. Endothelium-derived relaxing and contracting factors. FASEB J 1989; 3: 2007–18PubMedGoogle Scholar
  34. 34.
    Luscher TF, Vanhoutte PM. The endothelium: modulator of cardiovascular function. Boca Raton (FL): CRC Press, 1990Google Scholar
  35. 35.
    Kelm M, Schrader J. Control of coronary vascular tone by nitric oxide. Circ Res 1990; 66: 1561–75PubMedGoogle Scholar
  36. 36.
    Folkman J, Klagsbrun M. Anqioqenic factors. Science, 1987; 235: 442–7PubMedGoogle Scholar
  37. 37.
    Adair TH, Gay WJ, Montani J. Growth regulation of the vascular system: evidence for a metabolic hypothesis. Am J Physiol 1990; 259: R393–04PubMedGoogle Scholar
  38. 38.
    Davies PF, Tripathi SC. Mechanical stress mechanisms and the cell: an endothelial paradigm. Circ Res 1993; 72: 239–45PubMedGoogle Scholar
  39. 39.
    Benyo Z, Kiss G, Szabo C, et al. Importance of basal nitric oxide synthesis in regulation of myocardial blood flow. Car-diovasc Res 1991; 25: 70–03Google Scholar
  40. 40.
    Flavahan NA. Atherosclerosis or lipoprotein-induced endothelial dysfunction: potential mechanisms underlying reduction in EDRF/nitric oxide activity. Circulation 1992; 85: 1927–38PubMedGoogle Scholar
  41. 41.
    Malek AM, Izumo S. Molecular aspects of signal transduction of shear stress in the endothelial cell. J Hypertens 1994; 12: 989–99PubMedGoogle Scholar
  42. 42.
    Cohen RA, Vanhoutte PM. Endothelium-dependent hyperpolarization. Circulation 1995; 92: 3337–49PubMedGoogle Scholar
  43. 43.
    Moncada S, Palmer RMJ, Higgs EA. Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol 1989: 38: 1709–15PubMedGoogle Scholar
  44. 44.
    Palmer RMJ, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987; 327: 524–6PubMedGoogle Scholar
  45. 45.
    Kuo L, Davis MJ, Chilian WM. Endothelium-dependent, flow-induced dilation of isolated coronary arterioles. Am J Physiol 1990; 259: H1063–70PubMedGoogle Scholar
  46. 46.
    Altman JD, Kinn J, Duncker DJ, et al. Effect of inhibition of nitric oxide formation on coronary blood flow during exercise in the dog. Cardiovasc Res 1994; 28: 119–24PubMedGoogle Scholar
  47. 47.
    Parent R, Pare R, Lavallee M. Contribution of nitric oxide to dilation of resistance coronary vessels in conscious dogs. Am J Physiol 1992: 262: H10–16PubMedGoogle Scholar
  48. 48.
    Berdeaux A, Ghaleh B, Dubois-Rande JL, et al. Role of vascular endothelium in exercise-induced dilation of large epicardial coronary arteries in conscious dogs. Circulation 1994; 89: 2799–808PubMedGoogle Scholar
  49. 49.
    Rubanyi GM, Romero JC, Vanhoutte PM. Flow-induced release of endothelium-derived relaxing factor. Am J Physiol 1986; 250: H1145–9PubMedGoogle Scholar
  50. 50.
    Hintze TH, Vatner SF. Reactive dilation of large coronary arteries in conscious dogs. Circ Res 1984; 54: 50–7PubMedGoogle Scholar
  51. 51.
    Pohl U, Holtz J, Busse R, et al. Crucial role of endothelium in the vasodilation response to increased flow in vivo. Hypertension 1986; 8: 37–44PubMedGoogle Scholar
  52. 52.
    Segal SS. Communication among endothelial and smooth muscle cells coordinates blood flow control during exercise. News Physiol Sci 1992; 7: 152–6Google Scholar
  53. 53.
    Beny J, Pacicca C. Bidriectional electrical communication between smooth muscle and endothelial cells in the pig coronary artery. Am J Physiol 1994; 266: H1465–72PubMedGoogle Scholar
  54. 54.
    Kuo L, Davis MJ, Chilian WM. Endothelial modulation of arterial tone. News Physiol Sci 1992; 7: 5–9Google Scholar
  55. 55.
    Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991; 43: 109–42PubMedGoogle Scholar
  56. 56.
    Yamabe H, Okumura K, Ishizaka H, et al. Role of endothelium-derived nitric oxide in myocardial reactive hyperaemia. Am J Physiol 1992; 263: H8–H14PubMedGoogle Scholar
  57. 57.
    Gattullo D, Pagliaro P, Linden RJ, et al. The role of nitric oxide in the initiation and in the duration of some vasodilator responses in the coronary circulation. Pflugers Arch 1995; 430: 96–104PubMedGoogle Scholar
  58. 58.
    Gurevicius J, Salem MR, Metwally AA, et al. Contribution of nitric oxide to coronary vasodilation during hypercapnia ac-idosis. Am J Physiol 1995; 268: H39–47PubMedGoogle Scholar
  59. 59.
    Duncker DJ, Bache RJ. Inhibition of nitric oxide production aggravates myocardial hypoperfusion during exercise in the presence of a coronary artery stenosis. Circ Res 1994; 74: 629–40PubMedGoogle Scholar
  60. 60.
    Chu A, Chambers DE, Lin C, et al. Effects of inhibition of nitric oxide formation on basal vasomotion and endothelium-dependent responses of the coronary arteries in awake dogs. J Clin Invest 1991; 87: 1964–8PubMedGoogle Scholar
  61. 61.
    Goodson AR, Leibold JM, Gutterman DD. Inhibition of nitric oxide synthesis augments centrally induced sympathetic coronary vasoconstriction in cats. Am J Physiol 1994; 267: H1272–8PubMedGoogle Scholar
  62. 62.
    Lefroy DC, Crake T, Uren NG, et al. Effect of inhibition of nitric oxide synthesis on epicardial coronary artery caliber and coronary blood flow in humans. Circulation 1993: 88: 43–54PubMedGoogle Scholar
  63. 63.
    Kirkeboen KA, Naess PA, Offstad J, et al. Effects of regional inhibition of nitric oxide synthesis in intact porcine hearts. Am J Physiol 1994; 266: H1516–27PubMedGoogle Scholar
  64. 64.
    Offstad J, Naess PA, Aksnes G, et al. Nitric oxide regulates coronary blood flow at various coronary arterial pressures in intact porcine hearts. Acta Physiol Scand 1995; 154: 93–102PubMedGoogle Scholar
  65. 65.
    Brown IP, Thompson CI, Belloni FL. Role of nitric oxide in hypoxic coronary vasodilation in isolated perfused guinea pig heart. Am J Physiol 1993; 264: H821–9PubMedGoogle Scholar
  66. 66.
    Park KH, Rubin LE, Gross SS, et al. Nitric oxide is a mediator of hypoxic coronary vasodilation: relation to adenosine and cyclooxygenase-derived metabolites. Circ Res 1992; 71: 992–1001PubMedGoogle Scholar
  67. 67.
    Ueeda M, Silvia SK, Olsson RA. Nitric oxide modulates coronary autoregulation in the guinea pig. Circ Res 1992; 70: 1296–303PubMedGoogle Scholar
  68. 68.
    Pohl U, Lamontagne D, Bassenge E, et al. Attenuation of coronary autoregulation in the isolated rabbit heart by endothe-lium derived nitric oxide. Cardiovas Res 1994; 28: 414–9Google Scholar
  69. 69.
    Lamontagne D, Pohl U, Busse R. NG-nitro-L-arginine antagonizes endothelium-dependent dilator responses by inhibiting endothelium-derived relaxing factor release in the isolated rabbit heart. Pflugers Arch 1991; 418: 266–70PubMedGoogle Scholar
  70. 70.
    Smith REA, Palmer RMJ, Bucknall CA, et al. Role of nitric oxide synthesis in the regulation of coronary vascular tone in the isolated perfused rabbit heart. Cardiovas Res 1992; 26: 508–12Google Scholar
  71. 71.
    Amezcua JL, Palmer RMJ, de Souza BM, et al. Nitric oxide synthesized from L-arginine regulates vascular tone in the coronary circulation of the rabbit. Br J Pharmacol 1989; 97: 1119–24PubMedGoogle Scholar
  72. 72.
    Jones CJH, Kuo L, Davis MJ, et al. Role of nitric oxide in the coronary microvascular responses to adenosine and increased metabolic demand. Circulation 1995; 91: 1807–13PubMedGoogle Scholar
  73. 73.
    Kuo L, Chilian WM, Davis MJ. Interaction of pressure- and flow-induced responses in porcine coronary resistance vessels. Am J Physiol 1991; 261: H1706–15PubMedGoogle Scholar
  74. 74.
    Kostic MM, Schrader J. Role of nitric oxide in reactive hyperemia of the guinea pig heart. Circ Res 1992; 70: 208–12PubMedGoogle Scholar
  75. 75.
    Lamontagne D, Pohl U, Busse R. Mechanical deformation of vessel wall and shear stress determine the basal release of endothelium-derived relaxing factor in the intact rabbit coronary vascular bed. Circ Res 1992; 70: 123–30PubMedGoogle Scholar
  76. 76.
    Wang J, Wolin MS, Hintze TH. Chronic exercise enhances endotheliummediated dilation of epicardial coronary artery in conscious dogs. Circ Res 1993; 73: 829–38PubMedGoogle Scholar
  77. 77.
    Chilian WM, Eastham CL, Marcus ML. Microvascular distribution of coronary vascular resistance in beating left ventricle. Am J Physiol 1986; 251: H779–88PubMedGoogle Scholar
  78. 78.
    Meredith IT, Yeung AC, Weidinger FF, et al. Role of impaired endothelium-dependent vasodilation in ischemie manifestations of coronary artery disease. Circulation 1993; 87 Suppl. V: V56–66Google Scholar
  79. 79.
    Holtz J, Fostermann U, Pohl U, et al. Flow dependent, endothelium-mediated dilation of epicardial coronary arteries in conscious dogs. J Cardiovasc Pharmacol 1984; 6: 1161–9PubMedGoogle Scholar
  80. 80.
    Gaglione A, Hess OM, Felder L, et al. Effect of papaverine and exercise on proximal and distal coronary arteries. Coronary Artery Dis 1991; 2: 433–41Google Scholar
  81. 81.
    Cox DA, Vita JA, Treasure CB, et al. Atherosclerosis impairs flowmediated dilation of coronary arteries in humans Circulation 1989; 80: 458–65Google Scholar
  82. 82.
    Block AJ, Poole S, Vane JR. Modification of basal release of prostaglandins from rabbit isolated hearts. Prostaglandins 1974; 7: 473–86PubMedGoogle Scholar
  83. 83.
    Needleman P. The synthesis and function of prostaglandins in the heart. Fed Proc 1976; 35: 2376–81PubMedGoogle Scholar
  84. 84.
    Schror K, Moncada S, Ubatuba FB, et al. Transformation of arachidonic acid and prostaglandin endoperoxides by the guinea pig heart. Eur J Pharmacol 1978; 47: 103–14PubMedGoogle Scholar
  85. 85.
    Afonso S, Bandow GT, Rowe GG. Indomethacin and the prostaglandin hypothesis of coronary blood flow regulation. J Physiol (Lond) 1974; 241: 299–308Google Scholar
  86. 86.
    Alexander RW, Kent KM, Pasano JJ, et al. Regulation of postocclusive hyperemia by endogenously synthesized prostaglandins in the dog heart. J Clin Invest 1975; 55: 1174–81PubMedGoogle Scholar
  87. 87.
    Hintze TH, Kaley G. Prostaglandins and the control of blood flow in the canine myocardium. Circ Res 1977; 40: 313–20PubMedGoogle Scholar
  88. 88.
    Olsson RA, Bunger R, Spaan JAE. Coronary circulation. In: Fozzard HA, Jennings RB, Haber E, et al., editors. The heart and cardiovascular system: scientific foundations. Vol. II. New York: Raven Press Publishers, 1992: 1393–426Google Scholar
  89. 89.
    Boger RH, Bode-Boger SM, Schroder EP, et al. Increased prostacyclin production during exercise in untrained and trained men: effect of low-dose aspirin. J Appl Physiol 1995; 78: 1832–8PubMedGoogle Scholar
  90. 90.
    Dai XZ, Bache RJ. Effect of indomethacin on coronary blood flow during graded treadmill exercise in the dog. Am J Physiol 1984; 247: H452–58PubMedGoogle Scholar
  91. 91.
    Edlund A, Sollevi A, Wennmalm A. The role of adenosine and prostacyclin in coronary flow regulation in healthy man. Acta Physiol Scand 1989; 135: 39–46PubMedGoogle Scholar
  92. 92.
    Sessa WC, Pritchard K, Seyedi N, et al. Chronic exercise in dogs increases coronary vascular nitric oxide production and endo-thelial cell nitric oxide synthase gene expression. Circ Res 1994; 74: 349–53PubMedGoogle Scholar
  93. 93.
    Miller VM, Vanhoutte PM. Enhanced release of endothelium-derived factors by chronic increases in blood flow. Am J Physiol 1988; 255: H446–51PubMedGoogle Scholar
  94. 94.
    Rogers PJ, Miller DT, Bauer BA, et al. Exercise training and responsiveness of isolated coronary arteries. J Appl Physiol 1991; 71: 2346–51PubMedGoogle Scholar
  95. 95.
    Oltman CL, Parker JL, Laughlin MH. Endothelium-dependent vasodilation of proximal coronary arteries from exercise trained pigs. J Appl Physiol 1995; 79: 33–40PubMedGoogle Scholar
  96. 96.
    Laughlin MH, Mattox ML, Parker JL. Training-induced reduction of acetylcholine-mediated relaxation in rat coronary artery: proximal vs distal coronary responses. FASEB J 1992; 6: A1465Google Scholar
  97. 97.
    Booth FW, Thomason DB. Molecular and cellular adaptation of muscle in response to exercise: perspectives of various models. Physiol Rev 1991; 71: 541–86PubMedGoogle Scholar
  98. 98.
    Saltin B, Gollnick PD. Skeletal muscle adaptability: significance for metabolism and performance. Handbook of Physiology. Skeletal muscle. Bethesda (MD): Am Physiol Soc 1983, 555–631Google Scholar
  99. 99.
    Müller JM, Myers PR, Laughlin MH. Vasodilator responses of coronary resistance arteries of exercise trained pigs. Circulation 1994; 89: 2308–14PubMedGoogle Scholar
  100. 100.
    Parker JL, Oltman CL, Müller JM, et al. Effects of exercise training on regulation of tone in coronary arteries and arteri-oles. Med Sci Sports Exerc 1994; 26: 1252–61PubMedGoogle Scholar
  101. 101.
    Laughlin MH, Amann JF, Thorne PM, et al. Up-regulation of nitric oxide synthase in coronary resistance arteries isolated from exercise trained pigs [abstract]. Circulation 1994; 90: 1576Google Scholar
  102. 102.
    Hsieh HJ, Li NQ, Frangos JA. Shear-induced platelet-derived growth factor gene expression in human endothelial cells is mediated by protein kinase C. J Cell Physiol 1992; 150: 552–8PubMedGoogle Scholar
  103. 103.
    Malek AM, Gibbons GH, Dzau VJ, et al. Fluid shear stress differentially modulates expression of genes encoding basic fibroblast growth factor and platelet-derived growth factor B chair in vascular endothelium. J Clin Invest 1993; 92: 2013–21PubMedGoogle Scholar
  104. 104.
    Mitsumata M, Fishel RS, Nerem RM, et al. Fluid shear stress stimulate platelet-derived growth factor expression in endothelial cells. Am J Physiol 1993; 265: H3–8PubMedGoogle Scholar
  105. 105.
    Nishida K, Harrison DG, Navas JP, et al. Molecular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase. J Clin Invest 1992; 90: 2092–6PubMedGoogle Scholar
  106. 106.
    Noris M, Morigi M, Donadelli R, et al. Nitric oxide synthesis by cultured endothelial cells is modulated by flow conditions. CircRes 1995; 76: 536–43Google Scholar
  107. 107.
    Ranjan V, Xiao Z, Diamond SL. Constitutive NOS expression in cultured endothelial cells is elevated by fluid shear stress. Am J Physiol 1995; 269: H550–5PubMedGoogle Scholar
  108. 108.
    Frangos JA, Eskin SG, Mclntire LV, et al. Flow effects on prostacyclin production by cultured human endothelial cells. Science 1985; 227: 1477–9PubMedGoogle Scholar
  109. 109.
    Grabowshi EF, Jaffer EA, Weksler BB. Prostacyclin production by cultured endothelial cell monolayers exposed to step increases in shear stress. J Lab Clin Med 1985; 105: 36–43Google Scholar
  110. 110.
    Heistad DD, Armstrong ML, Marcus ML, et al. Augmented responses to vasoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys. Circ Res 1984; 54: 711–8PubMedGoogle Scholar
  111. 111.
    Shimokawa H, Tomoike H, Nabeyama S, et al. Coronary artery spasm induced in atherosclerotic miniature swine. Science 1983; 221: 560–2PubMedGoogle Scholar
  112. 112.
    Selke, FW, Armstrong ML, Harrison DG. Endothelium-dependent vascular relaxation is abnormal in the coronary microcirculation of atherosclerotic primates. Circulation 1990; 81: 1586–93Google Scholar
  113. 113.
    Chilian WM, Dellsperger RC, Layne SM, et al. Effects of atherosclerosis on the coronary microcirculation. Am J Physiol 1990; 258: H529–39PubMedGoogle Scholar
  114. 114.
    Motz W, Vogt M, Rabenau O, et al. Evidence of endothelial dysfunction in coronary resistance vessels in patients with angina pectoris and normal coronary angiograms. Am J Car-diol 1991; 68: 996–1003Google Scholar
  115. 115.
    Sambuceti G, Marzullo P, Giorgetti A, et al. Global alteration in perfusion response to increasing oxygen consumption in patients with single-vessel coronary artery disease. Circulation 1994; 90: 1696–705PubMedGoogle Scholar
  116. 116.
    Cohen RA, Zitnay RM, Haudenschild CC, et al. Loss of selective endothelial cell vasoactive functions caused by hyper-cholesterolemia in pig coronary arteries. Circ Res 1988; 63: 903–10PubMedGoogle Scholar
  117. 117.
    Creager MA, Cooke JP, Mendelsohn ME, et al. Hypercholesterolemia attenuates endothelium mediated vasodilation in man. J Clin Invest 1990; 86: 228–34PubMedGoogle Scholar
  118. 118.
    McLenachan JM, Williams JW, Fish RD, et al. Loss of flow-mediated endothelium-dependent dilation occurs early in the development of atherosclerosis. Circulation 1991; 84: 1273–8PubMedGoogle Scholar
  119. 119.
    Kuo L, Davis MJ, Cannon MS, et al. Pathophysiological consequences of atherosclerosis extend into the coronary micro-circulation. Restoration of endothelium-dependent responses by L-Arginine. Circ Res 1992; 70: 465–76PubMedGoogle Scholar
  120. 120.
    Uren NG, Crake T, Lefroy DC, et al. Reduced coronary vasodilator function in infarcted and normal myocardium after myocardial infarction. N Engl J Med 1994; 331: 222–7PubMedGoogle Scholar
  121. 121.
    Oltman CL, Parker JL, Adams HR, et al. Effects of exercise training on vasomotor reactivity of porcine coronary arteries. Am J Physiol 1992; 263: H372–82PubMedGoogle Scholar
  122. 122.
    Czernin J, Barnard J, Sun KT, et al. Effect of short-term cardiovascular conditioning and low-fat diet on myocardial blood flow and flow reserve. Circulation 1995; 92: 197–204PubMedGoogle Scholar
  123. 123.
    Meyer Jr DJ, Huxley VH. Capillary hydraulic conductivity is elevated by cGMP-dependent vasodilators. Circ Res 1992; 70: 382–91PubMedGoogle Scholar
  124. 124.
    Zhang R-S, Huxley VH. Control of capillary hydraulic conductivity via membrane potential dependent changes in Ca2+ influx. Am J Physiol 1992; 262: H144–8PubMedGoogle Scholar
  125. 125.
    Huxley VH, Williams DA, Laughlin MH. Differential permeability responses of isolated coronary arterioles in sedentary and exercise-trained pigs [abstract]. FASEB J 1994; 8: A840Google Scholar
  126. 126.
    Huxley VH, Williams DA, Laughlin MH. Isolated pig coronary arteriole protein permeability [abstract]. FASEB J 1994; 8: A1044Google Scholar
  127. 127.
    Gdwlowski DM, Duran WN. Dose-related effects of adenosine and bradykinin on microvascular permselectivity to macro-molecules in the hamster cheek pouch. Circ Res 1986; 58: 348–55Google Scholar
  128. 128.
    Huxley VH, Meyer Jr DJ. Capillary permeability: atrial peptide action is independent of passive Lp changes. Am J Physiol 1990; 259: H1351–6PubMedGoogle Scholar
  129. 129.
    Huxley VH, Tucker VL, Verbürg, et al. Increased capillary hydraulic conductivity induced by atrial natriuretic peptide. CircRes 1987; 60: 304–7Google Scholar
  130. 130.
    Huxley VH, Williams DA. Basal and adenosine-mediated protein flux from isolated coronary arterioles. Am J Physiol. In pressGoogle Scholar
  131. 131.
    Kimura M, Dietrich H, Huxley VH, et al. Measurement of hydraulic conductivity in isolated arterioles of rat brain cortex. Am J Physiol 1993; 264: H1788–97PubMedGoogle Scholar
  132. 132.
    Majno G, Palade GE. Studies on inflammation I. The effects of histamine and serotonin on vascular permeability. J Biophys BiochemCytol 1963; 11: 571–605Google Scholar
  133. 133.
    Meyer Jr DJ, Huxley VH. Differential sensitivity of exchange vessel hydraulic conductivity to atrial natriuretic peptide. Am J Physiol 1990; 258: H521–8PubMedGoogle Scholar
  134. 134.
    Olesen S-P, Crone C. Substances that rapidly augment ionic conductances of endothelium in cerebral venules. Acta Physiol Scand 1986; 127: 233–41PubMedGoogle Scholar
  135. 135.
    Laughlin MH. Coronary transport reserve in normal dogs. J Appl Physiol 1984; 57: 551–61PubMedGoogle Scholar
  136. 136.
    Laughlin MH. Effects of exercise training on coronary transport capacity. J Appl Physiol 1985; 58: 468–76PubMedGoogle Scholar
  137. 137.
    Laughlin MH, Diana JN. Myocardial transcapillary exchange in the hypertrophied heart of the dog. Am J Physiol 1975; 229: 838–46PubMedGoogle Scholar
  138. 138.
    Laughlin MH, Tomanek RJ. Myocardial capillarity and maximal capillary diffusion capacity in exercise-trained dogs. J Appl Physiol 1987; 63: 1481–6PubMedGoogle Scholar
  139. 139.
    Overholser KA, Laughlin MH, Bhatte M. Exercise traininginduced increase in coronary transport capacity. Med Sci Sports Exerc 1994; 26: 1239–44PubMedGoogle Scholar
  140. 140.
    Kassab GS, Fung YC. Topology and dimensions of pig coronary capillary network. Am J Physiol 1994; 267: H319–25PubMedGoogle Scholar
  141. 141.
    Smaje LH, Zweifach BW, Intaglietta M. Micropressures and capillary filtration coefficients in single vessels of cremaster muscle of the rat. Microvasc Res 1971; 2: 96–110Google Scholar
  142. 142.
    Svensjo E, Grega GJ. Evidence for endothelial cell-mediated regulation of macromolecule permeability by postcapillary venules. Fed Proc 1986; 45: 89–95PubMedGoogle Scholar
  143. 143.
    Starling EH. On the absorption of fluids from connective tissue spaces. J Physiol (Lond) 1896; 19: 312–26Google Scholar
  144. 144.
    Rous P, Gilding HP, Smith F. The gradient of vascular permeability. J Exp Med 1930; 51: 807–30PubMedGoogle Scholar
  145. 145.
    Anversa P, Giacomelli F, Wiener J. Regional variation in capillary permeability of ventricular myocardium. Microvasc Res 1973; 6: 273–85PubMedGoogle Scholar
  146. 146.
    McDonagh PF. Both protein and blood cells reduce coronary microvascular permeability to macromolecules. Am J Physiol 1983; 245: H698–706PubMedGoogle Scholar
  147. 147.
    Mann GE. Alterations of myocardial capillary permeability by albumin in the isolated, perfused rabbit heart. J Physiol (Lond) 1981; 319: 311–23Google Scholar
  148. 148.
    Duran WN, Alvarez AO, Yudilevich DL. Influence of maximal vasodilatation on glucose and sodium blood-tissue transport in canine heart. Microvasc Res 1973; 6: 347–59PubMedGoogle Scholar
  149. 149.
    Curry FE, Joyner WL, Rutledge JC. Graded modulation of frog micro vessel permeability to albumin using ionophore A23187. Am J Physiol 1992; 258: H587–98Google Scholar
  150. 150.
    Curry FE, Joyner WL. Modulation of capillary permeability: methods and measurements in individually perfused mammalian and frog microvessels. In: Ryan U, editor. Endothelial cells. Boca Raton (FL): CRC, 1988: 3–17Google Scholar
  151. 151.
    Williams DA, Huxley VH. Bradykinin-induced elevations of hydraulic conductivity display spatial and temporal variations in frog capillaries. Am J Physiol 1993; 264: H1575–81PubMedGoogle Scholar
  152. 152.
    Tucker VL, Huxley VH. Evidence for cholinergic regulation of microvessel hydraulic conductance during tissue hypoxia. Circ Res 1990; 66: 517–24PubMedGoogle Scholar
  153. 153.
    Fronek K, Zweifach BW. Pre- and post-capillary resistances in cat mesentery. Microvasc Res 1974; 7: 351–61PubMedGoogle Scholar
  154. 154.
    Hudlicka O, Growth of capillaries in skeletal muscle and cardiac muscle. Circ Res 1982; 50: 451–61PubMedGoogle Scholar
  155. 155.
    Hudlicka O. Development of microcirculation: capillary growth and adaptation. In: Renkin EM, Michel CC, editors. Handbook of physiology. Sec. 2: Circulation. Vol. IV. Microcirculation. Baltimore: Williams & Wilkins, 1984: 165–216Google Scholar
  156. 156.
    Breisch EA, White FC, Nimmo LE, et al. Exercise-induced cardiac hypertrophy: a correlation of blood flow and micro vas-culature. J Appl Physiol 1986; 60: 1259–67PubMedGoogle Scholar
  157. 157.
    Anversa P, Ricci R, Olivetti G. Effects of exercise on the capillary vasculature of the rat heart. Circulation 1987; 75 Suppl. 1: 112–118Google Scholar
  158. 158.
    Huxley VH, Turner KA. Elevation of in situ capillary hydraulic conductivity (Lp) by serotonin (5-HT) and calcitonin gene related peptide (CGRP) [abstract]. FASEB J 1993; 7: A535Google Scholar
  159. 159.
    Watanabe H, Kuhne W, Schwartz P, et al. A2-adenosine receptor stimulation increases macromolecule permeability of coronary endothelial cells. Am J Physiol 1992; 262: H1174–81PubMedGoogle Scholar
  160. 160.
    Crone C, Levitt DG. Capillary permeability to small solutes. In: Renkin EM, Michel CC, editors. Handbook of physiology. Sec. 2: Circulation. Vol. IV Microcirculation. Baltimore; Williams & Wilkins, 1984: 411–66Google Scholar
  161. 161.
    Curry FE. Mechanics and thermodynamics of transcapillary exchange. In: Renkin EM, Michel CC, editors. Handbook of physiology. Sec. 2: Circulation. Vol. IV Microcirculation. Baltimore: Williams & Wilkins, 1984: 309–74Google Scholar
  162. 162.
    Hornig B, Maier V, Drexler H. Physical training improves endothelial function in patients with chronic heart failure. Circulation 1995; 93: 210–4Google Scholar

Copyright information

© Adis International Limited 1996

Authors and Affiliations

  • M. H. Laughlin
    • 1
  • R. M. McAllister
    • 1
  • J. L. Jasperse
    • 1
  • S. E. Crader
    • 1
  • D. A. Williams
    • 1
  • V. H. Huxley
    • 1
  1. 1.Department of Veterinary Biomedical Sciences, Department of Physiology, and Dalton Cardiovascular Research CenterUniversity of MissouriColumbiaUSA

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