Endothelial Control of Shear Stress and Resistance in the Skeletal Muscle Microcirculation

  • Akos Koller
  • Gabor Kaley
Part of the Clinical Physiology Series book series (CLINPHY)


A hundred years ago, Thoma (84) suggested that a relationship exists between vessel diameter and flow in the same vessel. Experimental documentation of “flow-dependent” responses of blood vessels namely, an increase in diameter of large conduit arteries following increases in blood flow have already been described early in this century (11, 76). For a long time, however, locally released metabolic factors (1, 28, 65) and the myogenic response (2, 6, 33) were considered the two main peripheral regulatory mechanisms to control and maintain vascular resistance and thereby distribution of blood pressure and flow in microvascular networks. Although many physiological responses of microvessels could be explained satisfactorily based only on these two mechanisms, other could not; these include the rapid increase in collateral blood flow (73), and reactive (5, 50, 58) and functional hyperemia (22, 28) in skeletal muscle. Interestingly, all of these vascular reactions are accompanied by great increases in blood flow, but a causal relationship between the increase in flow itself and the decrease in resistance was not suspected to be an important factor during the development of these reactions.


Wall Shear Stress Blood Flow Velocity Reactive Hyperemia Wall Shear Rate Endothelium Derive Relaxing Factor 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Anrep, Von, G. On local vascular reactions and their interpretation. J. Physiol. Lond. 45: 318–327, 1912.Google Scholar
  2. 2.
    Bayliss, W. M. On the local reactions of the arterial wall to changes in internal pressure. J. Physiol (Lond.) 28: 220–231, 1902.Google Scholar
  3. 3.
    Bevan, J. A., and E. H. Joyce. Comparable sensitivity of flow contraction and relaxation to Na reduction may reflect flow-sensor characteristics. Am. J. Physiol. 263 (Heart Circ. Physiol. 32 ): H182 - H187, 1992.Google Scholar
  4. 4.
    Bevan, J. A., E. H. Joyce, and G. C. Wellman. Flow dependent dilation in a resistance artery still occurs after endothelium removal. Circ. Res. 63: 980–985, 1988.PubMedCrossRefGoogle Scholar
  5. 5.
    Bjornberg, J., U. Albert, and S. Mellander. Resistance responses in proximal arterial vessels, arterioles and veins during reactive hyperemia in skeletal muscle and their underlying regulatory mechanisms. Acta. Physiol. Scand. 139: 535–550, 1990.PubMedCrossRefGoogle Scholar
  6. 6.
    Borgstrom, P., P. O. Grande, and S. Mellander. A mathematical description of the myogenic response in the microcirculation. Acta. Physiol. Scand. 116: 363–376, 1982.PubMedCrossRefGoogle Scholar
  7. 7.
    Cooke, J. P., E. Rossitch, N. A. Andon, J. LosCazio, and V. J. DzAU. Flow activates an endothelial potassium channel to release an endogenous nitrovasodilator. J. Clin. Incest. 88: 1663–1671, 1991.CrossRefGoogle Scholar
  8. 8.
    Duling, B. R., and R. Berne. Propagated vasodilation in the microcirculation of the hamster cheek pouch. Circ. Res. 261: 163–170, 1970.CrossRefGoogle Scholar
  9. 9.
    Dull, R. O., and P. F. Davies. Flow modulation of agonist (Atp)-response (Ca2) coupling in vascular endothelial cells. Am. J. Physiol. 261 (Heart Circ. Physiol. 30 ): H149 - H154, 1991.Google Scholar
  10. 10.
    Falcone, J. C., M. J. Davis, and G. A. Meininger. Endothelial independence of myogenic response in isolated skeletal muscle arterioles. Am. J. Physiol. 260 (Heart Circ. Physiol. 29 ): H130 - H135, 1991.Google Scholar
  11. 11.
    Fleisch, A. Les réflexes nutritifs ascendants producteurs de dilatation arterielle. Arch. Int. Physiol. Biochem. 41: 141–167, 1935.Google Scholar
  12. 12.
    Frangos, J. A., S. G. Eskin, L. V. Mcintire, and C. L. Ives. Flow effects on prostacyclin production by cultured human endothelial cells. Science Wash. D.C. 227: 1477–1479, 1985.CrossRefGoogle Scholar
  13. 13.
    Fry, D. L. Hemodynamic forces in atherogenesis. In Cerebrouascular Diseases, P. Steinberg, ed. New York: Raven Press, 1976, pp. 77–95.Google Scholar
  14. 14.
    Funi, K., D. D. Heistad, and F. M. Faraci. Flow-mediated dilatation of the basilar artery in vivo. Circ. Res. 69: 697–705, 1991.CrossRefGoogle Scholar
  15. 15.
    Furchgott, R. F. Role of endothelium in responses of vascular smooth muscle. Circ. Res. 53: 557–573, 1983.PubMedCrossRefGoogle Scholar
  16. 16.
    Fung, Y. C. Microcirculation. In Biodynamics: Circulation. New York: Springer-Verlag, 1984.Google Scholar
  17. 17.
    Garcia-Roldan, J. L., and J. A. Bevan. Flow-induced constriction and dilation of cerebral resistance arteries. Circ. Res. 66: 1445–1448, 1990.CrossRefGoogle Scholar
  18. 18.
    Gerova, M., J. Gero, E. Barta, S. Dolezel, V. Smiesko, and V. Levieky. Neurogenic and myogenic control of conduit coronary: A possible interference. Basic Res. Cardiol. 76: 503–507, 1981.PubMedCrossRefGoogle Scholar
  19. 19.
    Griffith, T. M., and D. H. Edwards. Nitric oxide in arterial networks. In Nitric Oxide from L-arginine: A Bioregulatory System. S. Moncada and E. H. Higgs, eds. Amsterdam: Elsevier Science Publ. B. U. 1990, pp. 397–408.Google Scholar
  20. 20.
    Griffith, T. M., D. H. Edwards, R. L. I. Davies, T. J. Harrison, and K. T. Evans. Edrf coordinates the behavior of vascular resistance vessels. Nature Lond. 329: 442–445, 1987.PubMedCrossRefGoogle Scholar
  21. 21.
    Haggendal, E., N. J. Nilsson, and B. Norback. Effect of blood corpuscle concentration on cerebral blood flow. Acta. Chir. Scand. (suppl) 364: 3–12, 1966.Google Scholar
  22. 22.
    Hester, R. L., and B. R. Duling. Red cell velocity during functional hyperemia: implications for rheology and oxygen transport. Am. J. Physiol. 255 (Heart Circ. Physiol. 24 ): H236 - H244, 1988.Google Scholar
  23. 23.
    Hilton, S. M. A peripheral arterial conducting mechanism underlying dilation of the femoral artery and concerned in functional vasodilatation in skeletal muscle. J. Physiol. Lond. 149: 93–111, 1959.PubMedGoogle Scholar
  24. 24.
    Hintze, T. H., and S. F. Vatner. Reactive dilation of large coronary arteries in conscious dogs. Circ. Res. 54: 50–57, 1984.PubMedCrossRefGoogle Scholar
  25. 25.
    Holtz, J., U. Forstermann, U. Pohl, M. Giesler, B. Bassenge. Flow-dependent, endothelium-mediated dilation of epicardial arteries in conscious dogs: effects of cyclooxygenase inhibition. J. Cardiouasc. Pharmacol. 6: 1161–1169, 1984.Google Scholar
  26. 26.
    Hoogerwerf, N., P. J. W. Van Der Linden, N. Westerhohf, and P. Sipkema. A new mounting technique for perfusion of isolated small arteries: The effects of flow and oxygen on the diameter. Microvasc. Res. 44: 49–60, 1992.PubMedCrossRefGoogle Scholar
  27. 27.
    Hudak, M. L., M. D. Jones, JR., A. S. Popel, R. C. Koehler, R. J. Traystman, and S. L. Zeger. Hemodilution causes size-dependent constriction of pial arterioles in the cat. Am. J. Physiol. 257 (Heart Circ. Physiol. 26 ): H912 — H917, 1989.Google Scholar
  28. 28.
    Hudlicka, O., and F. EL Khelly. Metabolic factors involved in regulation of muscle blood flow. J. of Cardiovasc. Pharmacol. 7 (suppl. 3): 559–572, 1985.Google Scholar
  29. 29.
    Hull, S. S., JR., L. Kaiser, D. Jaffe, and H. V. Sparks, JR. Endothelium dependent flow induced dilation of canine femoral and saphenous arteries. Blood Vessels 23: 183–198, 1986.PubMedGoogle Scholar
  30. 30.
    Hutchins, G. M., M. M. Milner, and J. K. Boitnott. Vessel caliber and branch angle of human coronary artery branch points. Circ. Res. 38: 572–576, 1976.PubMedCrossRefGoogle Scholar
  31. 31.
    Ingerbrigsten, R., and S. Leraand. Dilation of a medium-sized artery immediately after local changes of blood pressure and flow measured by ultrasonic technique. Acta. Physiol. Scand. 79: 552–558, 1970.CrossRefGoogle Scholar
  32. 32.
    Inoue, T., H. ToMoike, K. Hisano, and M. Mohri. Endothelium functions as a flow sensor in reactive dilation of epicardial coronary artery in conscious dogs. Circulation 72: Iii - 81, 1985.Google Scholar
  33. 33.
    Johnson, P. C. The myogenic response. In Handbook of Physiology. The Cardiovascular System, Vascular Smooth Muscle. Bethesda, Md.: Am. Physiol. Soc.,1981, vol II, sec. 2, chapt. 15, p. 409–422.Google Scholar
  34. 34.
    Kaiser, L., and H. V. Sparks. Effect of hemodilution on endothelium-dependent vasodilation in the in vivo canine femoral artery. Circ. Shock 23: 107–118, 1987.PubMedGoogle Scholar
  35. 35.
    Kaley, G., A. Koller, J. M. Rodenburg, E. J. Messina, and M. S. Wolin. Regulation of arteriolar tone and responses via L-arginine pathway in skeletal muscle. Am. J. Physiology. 262 (Heart Circ. Physiol. 31 ): H987 — H992, 1992.Google Scholar
  36. 36.
    Kaley, G., J. M. Rodenburg, E. J. Messina, and M. S. Wolin. Endothelium-associated vasodilators in rat skeletal muscle microcirculation. Am. J.Physiol. (Heart Circ. Physiol. 25 ): H720 — H725, 1989.Google Scholar
  37. 37.
    Khayutin V. M., A. M. Melkumyants, A. N. Rogoza, E. S. Veselova, S. A. Balashov, and V. P. Nikolsky. Flow-induced control of arterial lumen. Acta. Physiol. Hung. 68: 241–251, 1986.PubMedGoogle Scholar
  38. 38.
    Koller, A., E. J. Messina, M. S. Wolin, and G. Kaley. Effects of endothelial impairment on arteriolar dilator responses in vivo. Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H1485 — H1489, 1989.Google Scholar
  39. 39.
    Koller, A., E. J. Messina, M. S. Wolin, and G. Kaley. Endothelial impairment inhibits prostaglandin and Edrf-mediated arteriolar dilation in vivo. Am. J. Physiol. 257 (Heart Circ. Physiol. 26 ): H1966 — H1970, 1989.Google Scholar
  40. 40.
    Koller, A., and G. Kaley. Flow velocity-dependent regulation of microvascular resistance in vivo. Microcirc. Endothelium and Lymphatics 5: 519–530, 1989.Google Scholar
  41. 41.
    Koller, A., and G. Kaley. Endothelium regulates skeletal muscle microcirculation by a blood flow velocity sensing mechanism. Am. J. Physiol. 258 (Heart Circ. Physiol. 27 ) H916 — H920, 1990.Google Scholar
  42. 42.
    Koller, A., and G. Kaley. Prostaglandins mediate arteriolar dilation to increased blood flow velocity in skeletal muscle microcirculation. Circ. Res. 67: 529–534, 1990.PubMedCrossRefGoogle Scholar
  43. 43.
    Koller, A., and G. Kaley. Role of endothelium in reactive dilation of skeletal muscle arterioles. Am. J. Physiol. 259 (Heart Circ. Physiol. 28 ): H1313 — H1316, 1990.Google Scholar
  44. 44.
    Koller, A., and G. Kaley. Endothelial regulation of wall shear stress and blood flow in skeletal muscle microcirculation. Am. J. Physiol. 260 (Heart Circ. Physiol. 29 ): H862 — H868, 1991.Google Scholar
  45. 45.
    Koller, A., and G. Kaley. Flow-dependent regulation in the microcirculation: Role of shear stress and endothelial prostaglandins. In Resistance Arteries, Structure and Function, M. J. Mulvany, et al., eds. Elsevier: Excerpta Medica, 1991, pp. 208–212.Google Scholar
  46. 46.
    Koller, A., N. Seyedi, M. E. Gerritsen, and G. Kaley. Edrf released from microvascular endothelial cells dilates arterioles in vivo. Am. J. Physiol. 261 (Heart Circ. Physiol. 30 ): H128 — H133, 1991.Google Scholar
  47. 47.
    Koller, A., J. M. Rodenburg, M. S. Wolin, E. J. Messina, and G. Kaley. Modified arteriolar responses to Atp after impairment of endothelium by light/dye techniques in vivo. Microvasc. Res. 41: 63–72, 1991.PubMedCrossRefGoogle Scholar
  48. 48.
    Koller, A., D. Sun, and G. Kaley. Role of shear stress and endothelial prostaglandins in flow-and viscosity-induced dilation of arterioles in vitro. Circ. Res. 72: 1276–1284, 1993.PubMedCrossRefGoogle Scholar
  49. 49.
    Koller, A., D. Sun, E. J. Messina, and G. Kaley. Effects of L-arginine analogs on dilator responses of isolated arterioles of rat skeletal muscle. Am. J. Physiol. (Heart Circ. Physiol. 33 ): H1194 — H1199, 1993.Google Scholar
  50. 50.
    KoNRaDI, G. P., and V. A. Levtov. Dependence of reactive hyperemia intensity on the occlusion duration in skeletal muscle. Fiziol. Zh. Kiev. 56: 366–374, 1970.Google Scholar
  51. 51.
    Kuo, L., W. M. Chilian, and M. J. Davis. Interaction of pressure-and flow-induced responses in porcine coronary resistance vessels. Am. J. Physiol. 261 (Heart Circ. Physiol. 30 ): H1706 — H1715, 1991.Google Scholar
  52. 52.
    Kuo, L., M. J. Davis, and W. M. Chilian. Endothelium-dependent, flow-induced dilation of isolated coronary arterioles. Am. J. Physiol. 259 (Heart Circ. Physiol. 28 ): H1063 — H1070, 1990.Google Scholar
  53. 53.
    Labarbera, M. Principles of design of fluid transport systems in zoology. Science 249: 992 1000, 1990.Google Scholar
  54. 54.
    Langille, B. L., and F. O’Donnell. Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science 231: 405–407, 1986.PubMedCrossRefGoogle Scholar
  55. 55.
    Lie, M., O. M. Sejersted, and F. Kill. Local regulation of vascular cross section during changes in femoral arterial blood flow in dogs. Circ. Res. 27: 727–737, 1970.PubMedCrossRefGoogle Scholar
  56. 56.
    Lipowsky, H. H., S. Kovalcheck, and B. W. Zweifach. The distribution of blood rheological parameters in the microvasculature of cat mesentery. Circ. Res. Vol 43, No. 5, 738–749, 1978.PubMedCrossRefGoogle Scholar
  57. 57.
    Lipowsky, H. H., and B. W. Zweifach. Methods for the simultaneous measurements of pressure differentials and flow in single unbranched vessels of the microcirculation for rheological studies. Microvasc. Res. 14: 345–361, 1977.PubMedCrossRefGoogle Scholar
  58. 58.
    Lombard, J. H., and B. R. Duling. Multiple mechanisms of reactive hyperemia in arterioles of the hamster cheek pouch. Am. J. Physiol. 241 (Heart Circ. Physiol. 10 ): H748 — H755, 1981.Google Scholar
  59. 59.
    Mayrovitz, H. N., and J. Roy. Microvascular blood flow: evidence indicating a cubic dependence on arteriolar diameter. Am. J. Physiol. 245 (Heart Circ. Physiol. 14 ): H1031 — H1038, 1983.Google Scholar
  60. 60.
    Meininger, G. A. Responses of sequentially branching macro and microvessels during reactive hyperemia in skeletal muscle. Microvasc. Res. 34: 29–45, 1987.PubMedCrossRefGoogle Scholar
  61. 61.
    Melkumyants, A. M., S. A. Balashov, and V. M. Khayutin. Endothelium dependent control of arterial diameter by blood viscosity. Cardiovasc. Res. 23: 741–747, 1989.PubMedCrossRefGoogle Scholar
  62. 62.
    Messina, E. J., R. Weiner, and G. Kaley. Arteriolar reactive hyperemia: modification by inhibitors of prostaglandin synthesis. Am. J. Physiol. 232 (6): H571 — H575, 1977.PubMedGoogle Scholar
  63. 63.
    Mo, M., S. C. Eskin, and W. P. Schilling. Flow induced changes in Cat+ signaling of vascular endothelial cells: effects of shear stress and Atp. Am. J. Physiol. 260 (Heart Circ. Physiol. 29 ): H1698 — H1707, 1991.Google Scholar
  64. 64.
    Murray, C. D. The physiological principle of minimum work. The vascular system and the cost of blood volume. Proc. Natl. Acad. Sci. U.S.A. 12: 207–214, 1926.PubMedCrossRefGoogle Scholar
  65. 65.
    Olsson, R. A., J. A. Snow, and M. K. Gentry. Adenosine metabolism in canine myocardial reactive hyperemia. Circ. Res. 42: 358–362, 1978.PubMedCrossRefGoogle Scholar
  66. 66.
    Palmer, R. M. J., A. G. Ferrige, and S. Moncada. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature Lond. 327: 524–526, 1987.PubMedCrossRefGoogle Scholar
  67. 67.
    PoHL, U., K. Herlan, A. Huang, and E. Bassange. Edrf-mediated shear-induced dilation opposes myogenic vasoconstriction in small rabbit arteries. Am. J. Physiol. 261 (Heart Circ. Physiol. 30 ): H2016–2023, 1991.Google Scholar
  68. 68.
    PoHL, U., J. Holtz, R. Busse, and E. Bassenge. Crucial role of endothelium in the vasodilator response to increases in flow in vivo. Hypertension Dallas 7: 37–44, 1986.Google Scholar
  69. 69.
    Quadt, J. F. A., R. Voss, and F. Tenhoor. Prostacyclin production of the isolated pulsatingly perfused rat aorta. J. Pharmacol. Meth. 7: 263–270, 1982.CrossRefGoogle Scholar
  70. 70.
    Ralevic, V., P. Milner, O. Hudlicka, F. Kristek, and G. Burnstock. Substance P is released from the endothelium of normal and capsaicin-treated rat hindlimb vasculature, in vivo, by increased flow. Circ. Res. 66: 1178–1183, 1990.PubMedCrossRefGoogle Scholar
  71. 71.
    Rodbard, S. Vascular caliber. Cardiology 60: 4–49, 1975.PubMedCrossRefGoogle Scholar
  72. 72.
    Rosenblum, W. I. Effects of blood pressure and blood viscosity on fluorescein transit time in the cerebral microcirculation in the mouse. Circ. Res. 27: 825–833, 1970.PubMedCrossRefGoogle Scholar
  73. 73.
    Rosenthal, S. L., and A. C. Guyton. Hemodynamics of collateral vasodilation following femoral artery occlusion in anesthetized dogs. Circ. Res. 23: 239–248, 1968.PubMedCrossRefGoogle Scholar
  74. 74.
    Rubanyi, G. M., J. C. Romero, and P. M. Vanhoutte. Flow-induced release of endothelium-derived relaxing factor. Am. J. Physiol. 250 (Heart Circ. Physiol. 19 ): H1145 – H1149, 1986.Google Scholar
  75. 75.
    Sakuma, I., D. Stuehr, S. S. Gross, C. Nathan, and R. Levi. Identification of arginine as a precursor of endothelium derived relaxing factor (Edrf). Proc. Natl. Acad. Sci. U.S.A. 85: 8664–8667, 1988.PubMedCrossRefGoogle Scholar
  76. 76.
    Schretzenmayr, A. Über kreislaufregulatorische Vorgänge an den grossen Arterien bei der Muskelarbeit. Pflügers Arch. 232: 743–748, 1933.CrossRefGoogle Scholar
  77. 77.
    Sherman, T. F., A. S. Popel, A. Koller, and P. C. Johnson. The cost of departure from optimal radii in microvascular networks. J. Theor. Biol. 136: 245–265, 1989.PubMedCrossRefGoogle Scholar
  78. 78.
    Sherman, T. F. On connecting large vessels to small. The meaning of Murray’s Law. J. Gen. Physiol. 78: 431–453, 1981.PubMedCrossRefGoogle Scholar
  79. 79.
    Sinoway, L. I., C. Hendrickson, W. R. Davidson, JR., S. Prophet, and R. Zelis. Characteristics of flow mediated brachial artery vasodilation in human subjects. Circ. Res. 64: 3242, 1989.CrossRefGoogle Scholar
  80. 80.
    Smiesko, V., J. Kozik, and S. Dolezel. Role of endothelium in the control of arterial diameter by blood flow. Blood Vessels 22: 247–251, 1985.PubMedGoogle Scholar
  81. 81.
    Smiesko, V., D. J. Lang, and P. C. Johnson. Dilator response of rat mesenteric arcading arterioles to increased blood flow velocity. Am. J. Physiol. 257 (Heart Circ. Physiol. 26 ): H1958 — H1965, 1989.Google Scholar
  82. 82.
    Sun, D., E. J. Messina, G. Kaley, and A. Koller. Characteristics and origins of the myogenic response in isolated mesenteric arterioles. Am. J. Physiol. 263 (Heart Circ. Physiol. 32 ): H1486 — H1491, 1992.Google Scholar
  83. 83.
    Tesfamariam, B., and W. Halpern. Modulation of adrenergic responses in pressurized resistance arteries by flow. Am. J. Physiol. (Heart Circ. Physiol. 22 ): H1112 — H1119, 1987.Google Scholar
  84. 84.
    Thoma, R. Untersuchungen über die Histogenese and Histomechanik des Gefässsystems. Stuttgart: F. Enke, 1893.Google Scholar
  85. 85.
    Vita, J. A., C. B. Treasure, P. Ganz, D. A. Cox, R. D. Fish, and A. P. Selwyn. Control of shear stress in the epicardial coronary arteries of humans: Impairment by atherosclerosis. J. Am. Coll. Cardiol. 14: 1193–1199, 1989.PubMedCrossRefGoogle Scholar
  86. 86.
    Wolin, M. S., J. M. Rodenburg, E. J. Messina, and G. Kaley. Similarities in the pharmacological modulation of reactive hyperemia and vasodilation to hydrogen peroxide in rat skeletal muscle arterioles: Effects of probes for endothelium-derived mediators. J. Pharmacol. Exptl. Ther. 253: 508–512, 1990.Google Scholar
  87. 87.
    Young, M. A., and S. F. Vatner. Blood flow and endothelium mediated vasomotion of iliac arteries in conscious dogs. Circ. Res. 61 (suppl. II): II-88–93, 1987.Google Scholar
  88. 88.
    Zamir, M. Shear forces and blood vessel radii in the cardiovascular system. J. Gen. Physiol. 69: 449–461, 1977.PubMedCrossRefGoogle Scholar

Copyright information

© American Physiological Society 1995

Authors and Affiliations

  • Akos Koller
  • Gabor Kaley

There are no affiliations available

Personalised recommendations