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Control of Skeletal Muscle Blood Flow During Dynamic Exercise

Contribution of Endothelium-Derived Nitric Oxide

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Summary

Traditional explanations for the hyperaemia which accompanies exercise have invoked the ‘metabolic theory’ of vasodilation, whereby contractile activity in the active muscle gives rise to metabolic by-products which dilate vessels bathed in interstitial fluid. Whilst metabolites with vasodilator properties have been identified, this theory does not adequately explain the magnitude of hyperaemia observed in active skeletal muscle, principally because large increases in flow are dependent on dilation of ‘feed’ arteries which lie outside the tissue parenchyma and are not subjected to changes in the interstitial milieu.

Coordinated resistance vessel dilation during exercise is therefore dependent on a signal which ‘ascends’ from the microvessels to the feed arteries located upstream. Recent studies of ascending vasodilation have concentrated on the possible contribution of the endothelium, a monolayer of flattened squamous cells which lie at the interface between the circulating blood and vascular wall. These cells are uniquely positioned to respond to changes in rheological and humoral conditions within the cardiovascular system, and to transduce these changes into vasoactive signals which regulate blood flow, vascular tone and arterial pressure.

Endothelial cells produce nitric oxide (NO), a rapidly diffusing labile substance which relaxes adjacent vascular smooth muscle. NO is released basally and contributes to the regulation of vascular tone by acting as a functional antagonist to sympathetic neural constriction. In addition, NO is spontaneously released in response to deformation of the endothelial cell membrane, indicating that changes in pulsatile flow and wall shear stress are likely physiological stimuli.

Since the dilation of microvessels in response to exercise increases blood flow through the upstream feed arteries, which subsequently dilate, one explanation for ascending vasodilation is that NO release is stimulated by flow-induced shear stress. Evidence that NO contributes to ascending vasodilation is reviewed, along with studies which indicate that NO mediates exercise hyperaemia, that physical conditioning upregulates NO production and that NO controls blood flow by modifying other physiological mechanisms.

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References

  1. Rowell LB. Human cardiovascular control. New York: Oxford University Press, 1993

    Google Scholar 

  2. Shepherd JT. Circulation to skeletal muscle. In: Shepherd JT, Abboud FM, Geiger SR, editors. Handbook of physiology. The cardiovascular system: peripheral circulation and organ blood flow. Vol. III. Part 1. Bethesda (MD): American Physiological Society, 1983: 319–70

    Google Scholar 

  3. Segal SS. Cell-to-cell communication coordinates blood flow control. Hypertension 1994; 23(Pt 2): 1113–20

    Article  PubMed  CAS  Google Scholar 

  4. Duling BR. The role of the resistance arteries in the control of peripheral resistance. In: Mulvany MJ, editor. Resistance arteries, structure and function. Amsterdam: Elsevier Science Publishers, 1991: 3–9

    Google Scholar 

  5. Gaskell WH. On the toxicity of the heart and vessels. J Physiol (Lond) 1880; 3: 48–75

    CAS  Google Scholar 

  6. Vanhoutte PM, Verbueren TJ, Webb RC. Local modulation of adrenergic neuroeffector interaction in the blood vessel wall. Physiol Rev 1981; 61: 151–247

    PubMed  CAS  Google Scholar 

  7. Sparks HVJ. Effect of local metabolic factors on vascular smooth muscle. In: Bohr DF, Somlyo AP, Sparks HVJ, et al, editors. Handbook of physiology. The cardiovascular system: vascular smooth muscle. Vol. II. Sect. 2. Bethesda (MD): American Physiological Society, 1980: 475–513

    Google Scholar 

  8. Wilson JR, Kapoor SC, Krishna GG. Contribution of potassium to exercise-induced vasodilation in humans. J Appl Physiol 1994; 77(6): 2552–7

    PubMed  CAS  Google Scholar 

  9. Lash JM. Contribution of arterial feed vessels to skeletal muscle functional hyperaemia. J Appl Physiol 1994; 76(4): 1512–9

    PubMed  CAS  Google Scholar 

  10. Segal SS. Communication among endothelial and smooth muscle cells coordinates blood flow control during exercise. News Physiol Sci 1992; 7: 152–6

    Google Scholar 

  11. Williams DA, Segal SS. Feed artery role in blood flow control to rat hindlimb skeletal muscles. J Physiol (Lond) 1993; 463: 631–46

    CAS  Google Scholar 

  12. Folkow B, Sonnenschein RR, Wright DL. Differential influences of nervous and local humoral factors on large and small precapillary vessels of skeletal muscle. In: Hudlicka O, editor. Circulation in skeletal muscle. New York: Pergamon Press, 1966: 165–9

    Google Scholar 

  13. Weideman MP, Tuma RF, Mayrovitz HM. Defining the precapillary sphincter. Microvasc Res 1976; 12: 71–5

    Article  Google Scholar 

  14. Delashaw JB, During BR. A study of the functional elements regulating capillary perfusion in striated muscle. Microvasc Res 1988; 36: 162–71

    Article  PubMed  CAS  Google Scholar 

  15. Savard GK, Richter EA, Strange S, et al. Norepinephrine spillover from skeletal muscle during exercise in humans: role of muscle mass. Am J Physiol 1989; 257: HI812–8

    Google Scholar 

  16. Esler M, Jennings G, Lambert G, et al. Overflow of catecholamine neurotransmitters to the circulation: source, fate, and functions. Physiol Rev 1990; 70: 963–85

    PubMed  CAS  Google Scholar 

  17. Rowell LB, Saltin B, Kiens B, et al. Is peak quadriceps blood flow in humans even higher during exercise with hypoxemia? Am J Physiol 1986; 251: H1038–44

    PubMed  CAS  Google Scholar 

  18. Rowell LB. Muscle blood flow in humans: how high can it go? Med Sci Sports Exerc 1988; 20(5): S97–103

    PubMed  CAS  Google Scholar 

  19. Segal SS, During BR. Communication between feed arteries and microvessels in hamster striated muscle: segmental vascular responses are functionally coordinated. Circ Res 1986; 59: 283–90

    Article  PubMed  CAS  Google Scholar 

  20. Granger HJ, Goodman AH, Granger DN. Role of resistance and exchange vessels in local microvascular control of skeletal muscle oxygenation in dogs. Circ Res 1976; 38: 379–85

    Article  PubMed  CAS  Google Scholar 

  21. Segal SS, Damon DN, During BR. Propogation of vasomotor responses coordinates arteriolar resistances. Am J Physiol 1989; 256: H832–7

    PubMed  CAS  Google Scholar 

  22. Krogh A, Harrop G A, Rehberg PB. Studies on the physiology of capillaries, III: the innervation of the blood vessel in the hind legs of the frog. J Physiol (Lond) 1922; 56: 179–89

    CAS  Google Scholar 

  23. Hilton SM. A peripheral arterial conducting mechanism underlying dilatation of the femoral artery and concerned in functional vasodilatation in skeletal muscle. J Physiol (Lond) 1959; 149:93–111

    CAS  Google Scholar 

  24. During BR, Berne RM. Propogated vasodilation in the micro-circulation of the hamster cheek pouch. Circ Res 1970; 26: 163–70

    Article  Google Scholar 

  25. Honig CR, Frearson JL. Neurons intrinsic to arterioles initiate postcontraction vasodilation. Am J Physiol 1976; 230: 493–507

    PubMed  CAS  Google Scholar 

  26. Segal SS. Microvascular recruitment in hamster striated muscle: role for conducted vasodilation. Am J Physiol 1991; 261: H181–9

    PubMed  CAS  Google Scholar 

  27. Segal SS, During BR. Conduction of vasomotor responses in arterioles: a role for cell-to-cell coupling? Am J Physiol 1989; 256: H838–45

    PubMed  CAS  Google Scholar 

  28. Segal SS, Bény J-L. Intracellular recording and dye transfer in arterioles during blood flow control. Am J Physiol 1992; 263: Hl–7

    Google Scholar 

  29. Mekata F. Current spread in the smooth muscle of the rabbit aorta. J Physiol (Lond) 1974; 242: 143–55

    CAS  Google Scholar 

  30. Bény J-L, Connat J-L. An electron microscopic study of smooth muscle cell dye coupling in the pig coronary arteries. Circ Res 1992; 70: 49–55

    Article  PubMed  Google Scholar 

  31. Hirst GDS, Neild TO. An analysis of excitatory junctional potentials recorded from arterioles. J Physiol (Lond) 1978; 280: 87–104

    CAS  Google Scholar 

  32. Koller A, Dawant B, Liu A, et al. Quantitative analysis of arteriolar network architecture in cat sartorius muscle. Am J Physiol 1987; 253: H154–64

    PubMed  CAS  Google Scholar 

  33. Koller A, Kaley G. Endothelial regulation of wall shear stress and blood flow in skeletal muscle microcirculation. Am J Physiol 1991; 260: H862–8

    PubMed  CAS  Google Scholar 

  34. Rodbard S. Vascular caliber. Cardiology 1975; 60: 4–49

    Article  PubMed  CAS  Google Scholar 

  35. Koller A, Kaley G. Endothelium regulates skeletal muscle microcirculation by a blood flow velocity-sensitive mechanism. Am J Physiol 1990; 258: H916–20

    PubMed  CAS  Google Scholar 

  36. Murray CD. The physiological principle of minimum work. The vascular system and the cost of blood volume. Proc Natl Acad Sci USA 1926; 12: 207–14

    Article  PubMed  CAS  Google Scholar 

  37. Zamir M. Shear stress forces and blood vessel radii in the cardiovascular system. J Gen Physiol 1977; 69: 449–61

    Article  PubMed  CAS  Google Scholar 

  38. Mayrovitz HN, Roy J. Microvascular blood flow: evidence indicating cubic dependence on arteriolar diameter. Am J Physiol 1983; 245: H1O31–8

    Google Scholar 

  39. Pohl U, Holtz J, Busse R, et al. Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension 1986; 8: 37–44

    Article  PubMed  CAS  Google Scholar 

  40. Rubanyi GM, Romero JC, Vanhoulle PM. Flow-induced release of endothelium-derived relaxing factor. Am J Physiol 1986; 250: H1145–9

    PubMed  CAS  Google Scholar 

  41. Folkow B, Sonnenschein RR, Wright DL. Loci of neurogenic and metabolic effects on precapillary vessels of skeletal muscle. Acta Physiol Scand 1971; 81: 459–71

    Article  PubMed  CAS  Google Scholar 

  42. Smiesko V, Lang DJ, Johnson PC. Dilator response of rat mes-enteric arcading arterioles to increased blood flow velocity. Am J Physiol 1989; 257: H1958–65

    PubMed  CAS  Google Scholar 

  43. Davignon J, Lorenz R, Shepherd JT. Response of human umbilical artery to changes in transmural pressure. Am J Physiol 1965; 209: 51–9

    Google Scholar 

  44. Falcone JC, Davis MJ, Meininger GA. Endothelial independence of myogenic response in isolated skeletal muscle arterioles. Am J Physiol 1991; 260: H130–5

    PubMed  CAS  Google Scholar 

  45. Folkow B. Description of the myogenic response. Circ Res 1964; 15:279–87

    PubMed  Google Scholar 

  46. Kuo L, Chilian WM, Davis MJ. Coronary arteriolar myogenic response is independent of the endothelium. Circ Res 1990; 66: 860–6

    Article  PubMed  CAS  Google Scholar 

  47. Griffith TM, Edwards DH. Myogenic autoregulation of flow may be inversely related to endothelium-derived relaxing factor activity. Am J Physiol 1990; 258: HI 171–80

    Google Scholar 

  48. Pohl U, Herlan K, Huang A, et al. EDRF-mediated shear-induced dilation opposes myogenic vasoconstriction in small rabbit arteries. Am J Physiol 1991; 261: H2016–23

    PubMed  CAS  Google Scholar 

  49. Calver A, Collier J, Vallance P. Nitric oxide and cardiovascular control. Exp Physiol 1993; 78: 303–26

    PubMed  CAS  Google Scholar 

  50. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature (Lond) 1980; 288: 373–6

    Article  CAS  Google Scholar 

  51. Furchgott RF. The role of endothelium in the responses of vascular smooth muscle to drugs. Annu Rev Pharmacol Toxicol 1984; 24: 175–97

    Article  PubMed  CAS  Google Scholar 

  52. Griffith TM, Edwards DH, Lewis MJ, et al. The nature of endothelium-derived relaxing factor. Nature 1984; 308: 645–7

    Article  PubMed  CAS  Google Scholar 

  53. Rubanyi GM, Lorenz RR, Vanhoutte PM. Bioassay of endothelium-derived relaxing factor(s): inactivation by catecholamines. Am J Physiol 1985; 249: H95–101

    PubMed  CAS  Google Scholar 

  54. Cocks TM, Angus JA, Campbell JH, et al. Release and properties of endothelium-derived relaxing factor (EDRF) from endothelial cells in culture. J Cell Physiol 1985; 123: 310–20

    Article  PubMed  CAS  Google Scholar 

  55. Gryglewski RJ, Palmer RMJ, Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 1986; 320: 454–6

    Article  PubMed  CAS  Google Scholar 

  56. Rubanyi GM, Vanhoutte PM. Superoxide anions and hyperxia inactivate endothelium-derived relaxing factor. Am J Physiol 1986; 250: H822–7

    PubMed  CAS  Google Scholar 

  57. Moncada S, Palmer RMJ, Gryglewski RJ. Mechanisms of action of some inhibitors of endothelium-derived relaxing factor. Proc Natl Acad Sci USA 1986; 88: 2166–70

    Article  Google Scholar 

  58. Martin W, Villani GM, Jothianandan D, et al. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by haemoglobin and by methylene blue in the rabbit aorta. J Pharmacol Exp Ther 1985; 232: 708–16

    PubMed  CAS  Google Scholar 

  59. Radomski MW, Palmer RMJ, Moncada S. Endogenous nitric oxide inhibits platelet adhesion to vascular endothelium. Lancet 1987; 2: 1057–8

    Article  PubMed  CAS  Google Scholar 

  60. Radomski MW, Palmer RMT, Moncada S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol 1987; 92: 181–7

    Article  PubMed  CAS  Google Scholar 

  61. Furchgott RF. Studies on relaxation of rabbit aorta by sodium nitrite: the basis for the proposal that the acidinactivable inhibitory factor from retractor penis is inorganic nitrite and that endothelium-derived relaxing factor is nitric oxide. In: Vanhoutte PM, editor. Vasodilatation: vascular smooth muscle, peptides, autonomic nerves and endothelium. New York: Raven Press, 1988:401–14

    Google Scholar 

  62. Ignarro LJ, Byrns RE, Wood KS. Biochemical auld pharmacological properties of endothelium-derived relaxing factor and its similarity to nitric oxide radical. In: Vanhoutte PM, editor. Vasodilatation: vascular smooth muscle, peptides, autonomic nerves and endothelium. New York: Raven Press, 1988: 739–49

    Google Scholar 

  63. Moncada S, Radomski RW, Palmer RMJ. Endothelium-derived relaxing factor: identification as nitric oxide and role in the control of vascular tone and platelet function. Biochem Pharmacol 1988; 37: 2495–501

    Article  PubMed  CAS  Google Scholar 

  64. Myers PR, Minor RLJ, Guerra RJ, et al. Vasorelaxant properties of endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide. Nature 1990; 345: 161–3

    Article  PubMed  CAS  Google Scholar 

  65. Feelisch M, te Poel M, et al. Understanding the controversy over the identity of EDRF. Nature 1994; 368: 62–5

    Article  PubMed  CAS  Google Scholar 

  66. Palmer RMJ, Rees DD, Ashton DS, et al. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun 1988; 153: 1251–6

    Article  PubMed  CAS  Google Scholar 

  67. Scott-Burden T. Regulation of nitric oxide production bytetrahydrobiopterin. Circulation 1995; 91(1): 248–50

    Article  PubMed  CAS  Google Scholar 

  68. Forstermann U, Closs EI, Pollock JS, et al. Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. Hypertension 1994; 23(2): 1121–31

    Article  PubMed  CAS  Google Scholar 

  69. Sessa WC, Pritchard K, Seyedi N, et al. Chronic exercise in dogs increases coronary vascular nitric oxide synthase production and endothelial cell nitric oxide synthase gene expression. Circ Res 1994; 74: 349–53

    Article  PubMed  CAS  Google Scholar 

  70. Elkarib AO, Sheng JJ, Betz AL, et al. The central effects of a nitric oxide synthase inhibitor (N-omeganitro-L-arginine) on blood pressure and plasma renin. Clin Exp Hypertens 1993; 15:819–32

    Article  CAS  Google Scholar 

  71. Toda N, Okamura T. Reciprocal regulation by putatively nitroxidergic and adrenergic nerves of monkey and dog temporal arterial tone. Am J Physiol 1991; 261: H1740–5

    PubMed  CAS  Google Scholar 

  72. Toda N, Okamura T. Role of nitric oxide in neurally induced cerebroarterial relaxation. J Pharmacol Exp Ther 1991; 258: 1027–32

    PubMed  CAS  Google Scholar 

  73. Yoshida K, Okamura T, Kimura H, et al. Nitric oxide synthase-immunoreactive nerve fibers in dog cerebral and peripheral arteries. Brain Res 1993; 629: 67–72

    Article  PubMed  CAS  Google Scholar 

  74. Nakane M, Schmidt HHHW, Pollock JS, et al. Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEBS Lett 1993; 316: 175–80

    Article  PubMed  CAS  Google Scholar 

  75. Kobzik L, Reid MB, Bredt DS, et al. Nitric oxide in skeletal muscle. Nature 1994; 372: 546–8

    Article  PubMed  CAS  Google Scholar 

  76. Forstermann U, Pollock JS, Schmidt HH, et al. Calmodulin-de-pendent endothelium-derived relaxing factor/nitric oxide synthase activity is present in particulate and cytosolic fractions of bovine aortic endothelial cells. Proc Natl Acad Sci USA 1991; 88: 1788–92

    Article  PubMed  CAS  Google Scholar 

  77. Marsden PA, Heng HHO, Scherer SW, et al. Structure and chromosomal location of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem 1993; 268: 17478–88

    PubMed  CAS  Google Scholar 

  78. Vallance P, Collier J, Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 1989; 2: 997–1000

    Article  PubMed  CAS  Google Scholar 

  79. Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 1991; 43(2): 109–42

    PubMed  CAS  Google Scholar 

  80. Malinski T, Taha Z, Grunfeld S, et al. Diffusion of nitric oxide in the aorta wall monitored in situ by polyphyrinic microsensors. Biochem Biophys Res Commun 1993; 193: 1076–82

    Article  PubMed  CAS  Google Scholar 

  81. Ignarro LJ, Adams JB, Horwitz PM, et al. Activation of soluble guanylate cyclase by NO-hemoproteins involves NO-heme exchange. J Biol Chem 1986; 261: 4997–5002

    PubMed  CAS  Google Scholar 

  82. Rapoport RM, Murad F. Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cGMP. Circ Res 1983; 52: 352–7

    Article  PubMed  CAS  Google Scholar 

  83. Lincoln TM, Cornwell TL. Intracellular cyclic GMP receptor proteins. FASEB J 1993; 7: 328–38

    PubMed  CAS  Google Scholar 

  84. Robertson BE, Schubert R, Hescheler J, et al. cGMP-dependent protein kinase activates Ca-activated K channels in cerebral artery smooth muscle cells. Am J Physiol 1993; 265:C229–303

    Google Scholar 

  85. Bolotina VM, Najibi S, Palacino JJ, et al. Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature 1994; 368: 850–3

    Article  PubMed  CAS  Google Scholar 

  86. Lee K, Greger JL, Consaul JR, et al. Nitrate, nitrite balance, and de novo synthesis of nitrate in humans consuming cured meats. Am J Clin Nutr 1986; 44: 188–94

    PubMed  CAS  Google Scholar 

  87. Leaf CD, Wishnok JS, Tannenbaum SR. Nitric oxide: the darkside. In: Moncada S, Higgs EA, editor. Nitric oxide from Larginine: a bioregulatory system. Amsterdam: Elsevier, 1990: 291–9

    Google Scholar 

  88. Wennmalm A, Edlund A, Petersson A-S. Analysis of nitrite as a marker for EDRF in human plasma [abstract]. Arch Int Pharmacology Ther 1990; 305: 292

    Google Scholar 

  89. Ignarro LJ. Biosynthesis and metabolism of endothelium-derived nitric oxide. Ann Rev Pharmacol Toxicol 1990; 30: 535–60

    Article  CAS  Google Scholar 

  90. Sagnella GA, Singer DRT, Markundan ND, et al. Atrial natriuretic peptide, cyclic GMP coupling and urinary sodium excretion during acute volume expansion in man. Can J Phys Pharm 1990; 68: 535–8

    Article  CAS  Google Scholar 

  91. Stamler JS, Jaraki O, Osbourne J, et al. Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc Natl Acad Sci USA 1992; 89: 7674–7

    Article  PubMed  CAS  Google Scholar 

  92. Stamler JS, Loh E, Roddy M-A, et al. Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans. Circulation 1994; 89: 2035–40

    Article  PubMed  CAS  Google Scholar 

  93. Rees DD, Palmer RMJ, Hodson HF, et al. A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol 1989; 96: 418–24

    Article  PubMed  CAS  Google Scholar 

  94. Yang Z, Richard V, Luscher T. Endothelium-derived nitric oxide in human aneries and veins. In: Moncada S, Higgs EA, editor. Nitric oxide from L-arginine: a bioregulatory system. Amsterdam: Elsevier, 1990: 89–93

    Google Scholar 

  95. Rees DD, Palmer RMT, Moncada S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci USA 1989; 86: 3375–8

    Article  PubMed  CAS  Google Scholar 

  96. Gardiner S, Compton AM, Bennet T, et al. Control of regional blood flow by endothelium-derived nitric oxide. Hypertension 1990; 15:486–92

    Article  PubMed  CAS  Google Scholar 

  97. Vallance R, Collier J, Moncada S. Nitric oxide synthesized from L-arginine mediates endothelium-derived dilatation of human veins. Cardiovasc Res 1989; 23: 1053–7

    Article  PubMed  CAS  Google Scholar 

  98. Ekelund U, Meilander S. Role of endothelium-derived nitricoxide in the regulation of tonus in large-bore arterial resistance vessels, arterioles and veins in cat skeletal muscle. Acta Physiol Scand 1990; 140: 301–9

    Article  PubMed  CAS  Google Scholar 

  99. Persson MG, Gustafsson LE, Wiklund NP, et al. Endogenous nitric oxide as a modulator of rabbit skeletal muscle micro circulation in vivo. BrJ Pharmacol 1990; 100: 463–6

    Article  CAS  Google Scholar 

  100. Kaley G, Koller A, Rodenburg JM, et al. Regulation of arteriolar tone and responses via L-arginine pathway in skeletal muscle. Am J Physiol 1992; 262: H987–92

    PubMed  CAS  Google Scholar 

  101. Ingebrigtsen R, Leraand S. Dilation of a medium-sized artery immediately after local changes of blood pressure and flow as measured by ultrasonic technique. Acta Physiol Scand 1970; 79: 552–8

    Article  PubMed  CAS  Google Scholar 

  102. Lie M, Sejersted OM, Kiil F. Local regulation of vascular cross section during changes in femoral arterial blood flow in dogs. Circ Res 1970; 27: 727–37

    Article  PubMed  CAS  Google Scholar 

  103. Hintze TH, Vatner SF. Reactive dilation of large coronary arteries in conscious dogs. Circ Res 1984; 54: 50–7

    Article  PubMed  CAS  Google Scholar 

  104. Smiesko V, Kozik J, Dolezel S. Role of endothelium in the control of arterial diameter by blood flow. Blood Vessels 1985; 22: 247–51

    PubMed  CAS  Google Scholar 

  105. Inoue T, Tomoike H, Hisano K, et al. Endothelium determines flow-dependent dilation of the epicardial coronary artery in dogs. J Am Coll Cardiol 1988; 11: 187–91

    Article  PubMed  CAS  Google Scholar 

  106. Holtz J, Forstermann U, Pohl U, et al. Flow-dependent, endothelium-mediated dilatation of epicardial coronary arteries in conscious dogs: effects of cyclooxygenase inhibition. J Cardiovasc Pharmacol 1984; 6: 1161–9

    PubMed  CAS  Google Scholar 

  107. Griffith TM, Edwards DH, Davies RL, et al. EDRF coordinates the behaviour of vascular resistance vessels. Nature 1987; 329: 442–5

    Article  PubMed  CAS  Google Scholar 

  108. Hutcheson IR, Griffith TM. Release of endothelium-derived relaxing factor is modulated both by frequency and amplitude of pulsatile flow. Am J Physiol 1991; 261: H257–62

    PubMed  CAS  Google Scholar 

  109. Kuo L, Chilian WM, Davis MJ. Interaction of pressure- and flow-induced responses in porcine coronary resistance vessels. Am J Physiol 1991; 261: H1706–15

    PubMed  CAS  Google Scholar 

  110. Koller A, Sun D, Huang A, et al. Co-release of nitric oxide and prostaglandins mediates flow-dependent dilation of rat gracilis muscle arterioles. Am J Physiol 1994; 267: H326–32

    PubMed  CAS  Google Scholar 

  111. Leibenman EH, Knab ST, Creager MA. Nitric oxide meditates vasodilator responses to flow in humans [abstract]. Circulation 1994; 90(4): I–138

    Google Scholar 

  112. Friebel M, Klotz KF, Ley K, et al. Flow-dependent regulation of arteriolar diameter in rat skeletal muscle in situ: role of endothelium-derived relaxing factor and prostanoids. J Physiol (Lond) 1995; 483(3): 715–26

    CAS  Google Scholar 

  113. 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: 123–30

    Article  PubMed  CAS  Google Scholar 

  114. 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: 2092–6

    Article  PubMed  CAS  Google Scholar 

  115. Uematsu M, Navas JP, Nishida K, et al. Mechanisms of endothelial cell NO synthase induction by shear stress [abstract]. Circulation 1993; 88(4): 1–184

    Google Scholar 

  116. Joannides R, Haefeli WE, Linder L, et al. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 1995; 91: 1314–9

    Article  PubMed  CAS  Google Scholar 

  117. Buga GM, Gold ME, Fukuto JM, et al. Shear stress-induced release of nitric oxide from endothelial cells grown on beads. Hypertension 1991; 17: 187–93

    Article  PubMed  CAS  Google Scholar 

  118. Cooke JP, Rossitch EJ, Andon NA, et al. Flow activates an endothelial potassium channel to release an endogenous nitrovasodilator. J Clin Invest 1991; 88: 1663–71

    Article  PubMed  CAS  Google Scholar 

  119. Oleson SP, Clapham DE, Davies PF. Haemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature (Lond) 1988; 331: 168–70

    Article  Google Scholar 

  120. Suarez J, Rubio R. Regulation of glycolytic flux by coronary flow in guinea pig heart. Role of vascular endothelial cell glycocalyx. Am J Physiol 1991; 261: H1994–2000

    PubMed  CAS  Google Scholar 

  121. Davies PF, Tripathi SC. Mechanical stress mechanisms and the cell: an endothelial paradigm. Circ Res 1993; 72: 239–45

    Article  PubMed  CAS  Google Scholar 

  122. Hecker M, Mulsch A, Bassenge E, et al. Vasoconstriction and increased flow: two principle mechanisms of shear stress dependent endothelial autacoid release. Am J Physiol 1993; 265: H828–33

    PubMed  CAS  Google Scholar 

  123. Lansman JB, Hallam TJ, Rink TJ. Single stretch-activated ion channels in vascular endothelial cells as mechanotransducers. Nature 1987; 325: 811–3

    Article  PubMed  CAS  Google Scholar 

  124. Falcone JC, Kuo L, Meininger GA. Endothelial cell calcium increases during flow-induced dilation in isolated arterioles. Am J Physiol 1993; 264: H653–9

    PubMed  CAS  Google Scholar 

  125. Mo M, Eskin SG, Schilling WR Flow-induced changes in Ca2+ signalling of vascular endothelial cells. Am J Physiol 1991; 260: 1698–707

    Google Scholar 

  126. Dull RO, Davies PF. Flow modulation of agonist (ATP)-response (Ca2+) coupling in vascular endothelial cells. Am J Physiol 1991; 261: H149–54

    PubMed  CAS  Google Scholar 

  127. Ando J, Kamatsuda T, Kamiya A. Cytoplasmic calcium response to fluid shear stress in cultured vascular endothelial cells in vitro. Cell Dev Biol 1990; 24: 871–7

    Article  Google Scholar 

  128. Shen J, Luscinskas FW, Connolly A, et al. Fluid shear stress modulates cytosolic free calcium in vascular endothelial cells. Am J Physiol 1992; 262: C384–90

    PubMed  CAS  Google Scholar 

  129. Ohno M, Gibbons GH, Dzau VJ, et al. Shear stress elevates endothelial cGMP. Circulation 1993; 88: 193–7

    Article  PubMed  CAS  Google Scholar 

  130. Kuchan MJ, Frangos JA. Role of calcium and calmodulin inflow-induced nitric oxide production in endothelial cells. Am J Physiol 1994; 266: C628–36

    PubMed  CAS  Google Scholar 

  131. Kuchan MJ, Jo H, Frangos JA. Role of G proteins in shear stress-mediated nitric oxide production by endothelial cells. Am J Physiol 1994; 267: C753–8

    PubMed  CAS  Google Scholar 

  132. Canty JM, Schwartz JS. Nitric oxide mediates flow-dependent epicardial coronary vasodilation to changes in pulse frequency but not mean flow in conscious dogs. Circulation 1994; 89: 375–84

    Article  PubMed  CAS  Google Scholar 

  133. Pollock JS, Klinghofer V, Forstermann U, et al. Endothelial nitric oxide synthase is myristolylated. FEBS Lett 1992; 309: 402–4

    Article  PubMed  CAS  Google Scholar 

  134. Sessa WC, Barber CM, Lynch KR. Mutation of N-myristoylation site converts endothelial cell nitric oxide synthase from a membrane to a cytosolic protein. Circ Res 1993; 72: 921–4

    Article  PubMed  CAS  Google Scholar 

  135. Noris M, Morigi M, Donadelli R, et al. Nitric oxide synthesis by cultured endothelial cells is modulated by flow conditions. Circ Res 1995; 76: 536–43

    Article  PubMed  CAS  Google Scholar 

  136. Awolesi M, Sessa WC, Sumpio B. Cyclic strain upregulates the endothelial cell nitric oxide synthase gene [abstract]. FASEB J 1993; 4360: 7

    Google Scholar 

  137. Shen W, Lundborg M, Wang J, et al. Role of EDRF in the regional blood flow and vascular resistance at rest and during exercise in conscious dogs. J Appl Physiol 1994; 77(1): 165–72

    PubMed  CAS  Google Scholar 

  138. Hirai T, Visneski MD, Kearns KJ, et al. Effects of NO synthase inhibition on the muscular blood flow response to treadmill exercise in rats. J Appl Physiol 1994; 77(3): 1288–93

    PubMed  CAS  Google Scholar 

  139. Sagach VF, Kindybalyuk AM, Kovalenko TN. Functional hyperaemia of skeletal muscle: role of endothelium. J Car-diovasc Pharmacol 1992; 20Suppl. 12: S170–5

    Article  CAS  Google Scholar 

  140. Kelley SS, Sparks HV. Endothelial cell dependent vasodilation in resistance vessels [abstract]. Physiologist 1986; 29: 180

    Google Scholar 

  141. Hussain SNA, Stewart DJ, Ludemann JP, et al. Role of endothelium-derived relaxing factor in active hyperaemia of the canine diaphragm. J Appl Physiol 1992; 72(6): 2393–401

    PubMed  CAS  Google Scholar 

  142. Hester RL, Eraslan A, Saito Y. Differences in EDNO contribution to arteriolar diameters at rest and during functional dilation in striated muscle. Am J Physiol 1993; 265: H146–51

    PubMed  CAS  Google Scholar 

  143. Ekelund U, Bjornberg J, Grände P-O, et al. Myogenic vascular regulation in skeletal muscle in vivois not dependent of endothelium-derived nitric oxide. Acta Physiol Scand 1992; 144: 199–207

    Article  PubMed  CAS  Google Scholar 

  144. Schwartz JS, Baran KW, Bache RJ. Effect of stenosis on exercise-induced dilation of large coronary arteries. Am Heart J 1990; 119:520–4

    Article  PubMed  CAS  Google Scholar 

  145. Parent R, Pare R, Lavalée M. Contribution of nitric oxide to dilation of resistance coronary vessels in conscious dogs. Am J Physiol 1992; 262: H10–6

    PubMed  CAS  Google Scholar 

  146. Wang J, Wolin MS, Hintze TH. Chronic exercise enhances endothelium-mediated dilation of epicardial coronary artery in conscious dogs. Circ Res 1993; 73: 829–38

    Article  PubMed  CAS  Google Scholar 

  147. Ishibashi Y, Duncker DJ, Klassen C, et al. Endogenous nitricoxide production contributes to coronary blood flow during exercise [abstract]. J Am Coll Cardiol 1995; Feb: 115A

    Google Scholar 

  148. Berdeaux A, Ghaleh B, Dubois-Randä JL, et al. Role of vascular endothelium in exercise-induced dilation of large epicardial coronary arteries in conscious dogs. Circulation 1994; 89: 2799–808

    Article  PubMed  CAS  Google Scholar 

  149. Maekawa K, Saito D, Obayashi N, et al. Role of endothelium-derived nitric oxide and adenosine in functional myocardial hyperaemia. Am J Physiol 1994; 267: H166–73

    PubMed  CAS  Google Scholar 

  150. Persson MG, Wiklund NP, Gustafsson LE. Nitric oxide requirement for vasomotor nerve-induced vasodilatation and modulation of resting blood flow in muscle microcirculation. Acta Physiol Scand 1991; 141: 49–56

    Article  PubMed  CAS  Google Scholar 

  151. Mugge A, Lopez JA, Picgors DJ, et al. Acetylcholine-induced vasodilatation in rabbit hindlimb in vivois not inhibited by analogues of L-arginine. Am J Physiol 1991; 260: H242–7

    PubMed  CAS  Google Scholar 

  152. Saito Y, Eraslan A, Hester RL. Role of EDRFs in the control of arteriolar diameter during increased metabolism of striated muscle. Am J Physiol 1994; 267: H195–200

    PubMed  CAS  Google Scholar 

  153. Vanhoutte PM, Miller VM. Heterogeneity of endothelium-dependent response in mammalian blood vessels. J Cardiovasc Pharmacol 1985; 7Suppl. 3: S12–23

    Article  PubMed  CAS  Google Scholar 

  154. Richard V, Berdeaux A, La Rochelle CD, et al. Regional coronary haemodynamic effects of two inhibitors of nitric oxide synthesis in anaesthetized, open-chested dogs. Br J Pharmacol 1991; 104:59–64

    Article  PubMed  CAS  Google Scholar 

  155. Ambring A, Benthin G, Petersson A-S, et al. Indirect evidence of increased expression of NO synthase in marathon runners, and upregulation of NO synthase activity during running [abstract]. Circulation 1994; 90(4): 1–137

    Google Scholar 

  156. Shear WS, Christensen BV, Iacarella CL, et al. Measurement of systemic nitric oxide release during exercise and its impairment in microvascular disease. Circulation 1994; 90(4): 1–496

    Google Scholar 

  157. Bode-Boger SM, Boger RH, Frolich JC. Exercise increases systemic nitric oxide production in men. J Am Coll Cardiol 1995; Feb: 298A

    Google Scholar 

  158. Gleim GW, Zeballos GA, Glace BW, et al. Venous nitric oxide decrease in highly trained endurance athletes during maximal exercise. Circulation 1994; 90(4): 1–659

    Google Scholar 

  159. Matsumoto A, Hirata Y, Momomura S, et al. Increased nitric oxide production during exercise. Lancet 1994; 343: 849–50

    Article  PubMed  CAS  Google Scholar 

  160. Whitney RJ. The measurement of volume changes in human limbs. J Physiol 1953; 121: 1–27

    PubMed  CAS  Google Scholar 

  161. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340: 1111–5

    Article  PubMed  CAS  Google Scholar 

  162. Johnson JM, Rowell LB. Forearm skin and muscle vascular responses to prolonged leg exercise in man. J Appl Physiol 1975; 39(6): 920–4

    PubMed  CAS  Google Scholar 

  163. Wilson JR, Kapoor S. Contribution of endothelium-derived relaxing factor to exercise-induced vasodilation in humans. J Appl Physiol 1993; 75(6): 2740–4

    PubMed  CAS  Google Scholar 

  164. Gilligan DM, Panza JA, Kilcoyne CM, et al. Contribution of endothelium-derived nitric oxide to exercise-induced vasodilation. Circulation 1994; 90: 2853–8

    Article  PubMed  CAS  Google Scholar 

  165. Calver A, Collier J, Moncada S, et al. Effect of intra-arterial NG-monomethyl-L-arginine in patients with hypertension: the nitric oxide dilator system appears impaired. J Hypertens 1992; 10: 1025–31

    Article  PubMed  CAS  Google Scholar 

  166. Endo T, Imaizumi T, Tagawa T, et al. Role of nitric oxide in exercise-induced vasodilation of the forearm. Circulation 1994; 90: 2886–90

    Article  PubMed  CAS  Google Scholar 

  167. Meredith IT, Jain RK, Anderson TJ, et al. Endothelium-derived nitric oxide contributes to exercise-induced hyperaemia in the human dream. Circulation 1994; 90(4): 1–295

    Google Scholar 

  168. Quyyumi AA, Dakak N, Andrews NP, et al. Contribution of nitric oxide to metabolic coronary vasodilation in the human heart. Circulation 1995; 92: 320–6

    Article  PubMed  CAS  Google Scholar 

  169. Zeiher AM, Krause T, Schachinger V, et al. Impaired endothelium-dependent vasodilation of coronary resistance vessels is associated with exercise-induced myocardial ischemia. Circulation 1995; 91: 2345–52

    Article  PubMed  CAS  Google Scholar 

  170. Miller VM, Aarhus LA, Vanhoutte PM. Modulation of endothelium-dependent responses by chronic alterations of blood flow. Am J Physiol 1986; 251: H520–7

    PubMed  CAS  Google Scholar 

  171. Miller VM, Vanhoutte PM. Enhanced release of endothelium-derived factor(s) by chronic increases in blood flow. Am J Physiol 1988; 255: H446–51

    PubMed  CAS  Google Scholar 

  172. Miller VM, Burnett JCJ. Modulation of NO and endothelin by chronic increases in blood flow in canine femoral arteries. Am J Physiol 1992; 263: H103–8

    PubMed  CAS  Google Scholar 

  173. DiCarlo SE, Blair RW, Bishop VS, et al. Daily exercise enhances coronary resistance vessel sensitivity to pharmacological activation. J Appl Physiol 1989; 66(1): 421–8

    PubMed  CAS  Google Scholar 

  174. Delp MD, McAllister RM, Laughlin MH. Exercise training alters endothelium-dependent vasoreactivity of rat abdominal aona. J Appl Physiol 1993; 75: 1354–63

    PubMed  CAS  Google Scholar 

  175. Sun D, Huang A, Koller A, et al. Short-term daily exercise activity enhances endothelial NO synthesis in skeletal muscle anerioles of rats. J Appl Physiol 1994; 76(5): 2241–7

    PubMed  CAS  Google Scholar 

  176. Koller A, Huang A, Sun D, et al. Exercise training augments flow-dependent dilation in rat skeletal muscle anerioles. Circ Res 1995; 76: 544–50

    Article  PubMed  CAS  Google Scholar 

  177. Chen H, Li H-T. Physical conditioning can modulate endothelium-dependent vasorelaxation in rabbits. Aterioscler Thromb 1993; 13:852–6

    Article  CAS  Google Scholar 

  178. Chen H, Li H-T, Chen C-C. Physical conditioning decreases norepinephrine-induced vasconconstriction in rabbits. Possible roles of norepinephrine-evoked endothelium-derived relaxing factor. Circulation 1994; 90: 970–5

    Article  PubMed  CAS  Google Scholar 

  179. Muller JD, Myers PR, Laughlin MH. Vasodilator responses of coronary resistance aneries of exercise-trained pigs. Circulation 1994; 89: 2308–14

    Article  PubMed  CAS  Google Scholar 

  180. Laughlin MH, Oltman CL, Muller JM, et al. Adaptation of coronary circulation to exercise training. In: Fletcher GF, editor. Cardiovascular response to exercise. Chapt. 10. Mount Kisco (NY): Futura Publishing Co, 1994

    Google Scholar 

  181. Saltin B, Blomqvist G, Mitchell JH, Johnson RLJ, Wildenthal K, Chapman CB. Response to exercise after bed rest and after training. Circulation 1968; 38Suppl. 7: 1–78

    Google Scholar 

  182. Rowell LB. Human cardiovascular adjustments to exercise and thermal stress. Physiol Rev 1974; 54: 75–159

    PubMed  CAS  Google Scholar 

  183. Clausen J-P. Effect of physical training on cardiovascular adjustments to exercise in man. Physiol Rev 1977; 57: 779–815

    PubMed  CAS  Google Scholar 

  184. Rowell LB. Human circulation: regulation during physical stress. New York: Oxford University Press, 1986

    Google Scholar 

  185. Gleser MA. Effects of hypoxia and physical training on hemodynamic adjustments to one-legged exercise. J Appl Physiol 1973; 34: 655–9

    PubMed  CAS  Google Scholar 

  186. Davies CTM, Sargeant AJ. Effects of training on the physiological responses to one- and two-leg work. J Appl Physiol 1975; 38:377–81

    PubMed  CAS  Google Scholar 

  187. Klausen K, Secher NH, Clausen JP, et al. Central and regional circulatory adaptations to one-legged training. J Appl Physiol 1982; 52: 976–83

    PubMed  CAS  Google Scholar 

  188. Galbo H. Hormonal and metabolic adaptation to exercise. NewYork: Thieme-Stratton, 1983

    Google Scholar 

  189. Sinoway LI, Shenberger J, Wilson J, et al. A 30-day forearm work protocol increases maximal forearm blood flow. J Appl Physiol 1987; 62(3): 1063–7

    PubMed  CAS  Google Scholar 

  190. Sinoway LI, Musch TI, Minotti JR, et al. Enhanced maximal metabolic vasodilation in the dominant forearms of tennis players. J Appl Physiol 1986; 61: 673–8

    PubMed  CAS  Google Scholar 

  191. Silber DH, Sinoway LI. Reversible impairment of forearm vasodilation after forearm casting. J Appl Physiol 1990; 68: 1945–9

    PubMed  CAS  Google Scholar 

  192. Shenberger JS, Leaman GJ, Zelis R, et al. Physiologic and structural indices of vascular function in paraplegics. Med Sci Sports Exerc 1990; 22: 96–101

    PubMed  CAS  Google Scholar 

  193. Snell PG, Martin WH, Buckey JC, et al. Maximal vascular leg conductance in trained and untrained men. J Appl Physiol 1987; 62: 606–10

    PubMed  CAS  Google Scholar 

  194. Smolander J. Forearm reactive hyperaemia in manual workers [abstract]. Acta Physiol Scand 1993; 149: 13A

    Google Scholar 

  195. Currens JH, White PD. Half century of running: clinical, physiological and autopsy findings in the case of Clarence De Mar, ‘Mr. Marathoner’. N Engl J Med 1961; 265: 988–93

    Article  PubMed  CAS  Google Scholar 

  196. Pellicia A, Spataro A, Granata J, et al. Coronary arteries in physiological hypertrophy: echocardiographic evidence of increased proximal size in elite athletes. Int J Sports Med 1990; 11: 120–6

    Article  Google Scholar 

  197. Rose G, Prineas RJ, Mitchell JRA. Myocardial infarction and the intrinsic calibre of coronary arteries. Br Heart J 1967; 29: 548–52

    Article  PubMed  CAS  Google Scholar 

  198. Mann GV, Spoerry A, Gray M, et al. Atherosclerosis in the Masi. Am J Epidemiol 1972; 95: 26–37

    PubMed  CAS  Google Scholar 

  199. Tepperman J, Pearlman D. Effects of exercise and anemia on coronary arteries of small animals as revealed by the corrosion-cast technique. Circ Res 1961; 9: 576–83

    Article  PubMed  CAS  Google Scholar 

  200. Leon AS, Bloor CM. Effects of exercise and its cessation on the heart and its blood supply. J Appl Physiol 1968; 24: 485–90

    PubMed  CAS  Google Scholar 

  201. Bloor CM, Leon AS. Interaction of age and exercise on the heart and its blood supply. Lab Invest 1970; 22: 160–5

    PubMed  CAS  Google Scholar 

  202. Kramsch DM, Aspen AJ, Abramowitz BM, et al. Reduction of coronary atherosclerosis by moderate conditioning exercise in monkeys on an atherogenic diet. N Engl J Med 1981; 305: 1483–9

    Article  PubMed  CAS  Google Scholar 

  203. Haskell WL, Sims C, Myell J, et al. Coronary artery size and dilating capacity in ultradistance runners. Circulation 1993; 87: 1076–82

    Article  PubMed  CAS  Google Scholar 

  204. Green DJ, Cable NT, Fox C, et al. Modification of forearm resistance vessels by exercise training in young men. J Appl Physiol 1994; 77(4): 1829–33

    PubMed  CAS  Google Scholar 

  205. Langille BL, O’Donnell F. Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Nature (Lond) 1986; 231: 405–7

    CAS  Google Scholar 

  206. Segal SS, Kurjiaka DT, Caston AL. Endurance training increases arterial wall thickness in rats. J Appl Physiol 1993; 74(2): 722–6

    PubMed  CAS  Google Scholar 

  207. Kamiya A, Togawa T. Adaptive regulation of wall shear- stress to flow change in the canine carotid artery. Am J Physiol 1980; 239: H14–21

    PubMed  CAS  Google Scholar 

  208. Guyton JR, Hartley CJ. Flow restriction of one carotid artery in juvenile rats inhibits growth of arterial diameter. Am J Physiol 1985; 248: H540–6

    PubMed  CAS  Google Scholar 

  209. Langille BL, Bendeck MP, Keeley FW. Adaptations of carotid arteries of young and mature rabbits to reduced carotid blood flow. Am J Physiol 1989; 256: H931–9

    PubMed  CAS  Google Scholar 

  210. Garg UC, Hassid A. Nitric-oxide generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 1989; 83: 1774–7

    Article  PubMed  CAS  Google Scholar 

  211. Hogan M, Cerami A, Bucala R. Advanced glycolysation end-products block the antiproliferative effect of nitric oxide: role in the vascular and renal complications of diabetes mellitus. J Clin Invest 1992; 90: 1110–5

    Article  PubMed  CAS  Google Scholar 

  212. Kolpakov V, Gordon D, Kulik TJ. Nitric oxide-generating compounds inhibit total protein and collagen synthesis in cultured vascular smooth muscle cells. Circ Res 1995; 76: 305–9

    Article  PubMed  CAS  Google Scholar 

  213. Tesfamariam B, Weisbrod RM, Cohen RA. Endothelium inhibits responses of rabbit carotid artery to adrenergic nerve stimulation. Am J Physiol 1987; 253: H792–8

    PubMed  CAS  Google Scholar 

  214. Tesfamariam B, Cohen RA. Inhibition of adrenergic vasoconstriction by endothelial shear stress. Circ Res 1988; 63: 720–5

    Article  PubMed  CAS  Google Scholar 

  215. Vo PA, Reid JJ, Rand MJ. Attenuation of vasoconstriction by endogenous nitric oxide in rat caudal artery. Br J Pharmacol 1992; 107: 1121–8

    Article  PubMed  CAS  Google Scholar 

  216. Thorin E, Atkinson J. Modulation by the endothelium of sympathetic vasoconstriction in an in vitropreparation of the rat tail artery. Br J Pharmacol 1994; 111:351–7

    Article  PubMed  CAS  Google Scholar 

  217. MacLean MR, Graham J, McGrath JC. Endogenous nitric oxide modulates vasopressor responses, but not depressor responses to spinal sympathetic nerve stimulation in pithed rats. J Cardiovasc Pharmacol 1994; 23: 319–25

    Article  PubMed  CAS  Google Scholar 

  218. Bortone A, Hess OM, Eberli FR, et al. Abnormal coronary vasomotion during exercise in patients with normal coronary arteries and reduced coronary flow reserve. Circulation 1989; 79:516–27

    Article  PubMed  CAS  Google Scholar 

  219. Zazinger J, Czachurski J, Sellar H. Inhibition of sympathetic vasoconstriction is a major principle of vasodilation by nitric oxide in vivo. Circ Res 1994; 75: 1073–7

    Article  Google Scholar 

  220. Vanhoutte PM, Miller VM. Alpha2-adrenoceptors and endothelium-derived relaxing factor. Am J Med 1989; 87Suppl. 3C: 1S–4S

    Article  PubMed  CAS  Google Scholar 

  221. Angus JA, Cocks TM, Satoh K. The α adrenoceptors on endothelial cells. Fed Proc 1986; 45: 2355–9

    PubMed  CAS  Google Scholar 

  222. Angus JA, Cocks TM, Satoh K. Alpha-2 adrenoceptors and endothelium-dependent relaxation in canine large arteries. Br J Pharmacol 1986; 88: 767–77

    Article  PubMed  CAS  Google Scholar 

  223. Miller VM. Interaction between neural and endothelial mechanisms in control of vascular tone. News Physiol Sci 1989; 6: 60–3

    Google Scholar 

  224. Miller VM, Flavahan NA, Vanhoutte PM. Penussis toxin reduces endothelium-dependent and independent responses to α2-adrenergic stimulation in systemic canine arteries and veins. J Pharmacol Exper Ther 1991; 257: H1127–31

    Google Scholar 

  225. Egleme C, Godfraind T, Miller RC. Enhanced responsiveness of rat isolated aorta to clonidine after removal of endothelial cells. Br J Pharmacol 1984; 81: 16–8

    Article  PubMed  CAS  Google Scholar 

  226. Lues I, Schumann H-J. Effect of removing the endothelial cells on the reactivity of rat aortic segments to different α-adrenoceptor agonists. Naunyn Schmeidebergs Arch Pharmakol 1984; 328: 160–3

    Article  CAS  Google Scholar 

  227. Cohen RA, Weisbrod RM. Endothelium inhibits norepinephrine release from adrenergic nerves of rabbit carotid artery. Am J Physiol 1988; 254: H871–8

    PubMed  CAS  Google Scholar 

  228. Feelisch M, Bloch W, Addicks K. Control of intraaxonal cate-cholamine storage in cardiac sympathetic nerve fibres by endogenous nitric oxide [Abstract]. Endothelium 1993; 1: 25

    Google Scholar 

  229. Chen C, Schofield GG. Nitric oxide modulates Ca2+ channel currents in rat sympathetic neurons. Eur J Pharmacol 1993; 243: 83–6

    Article  PubMed  CAS  Google Scholar 

  230. Itoh H, Takeda K, Tanaka M, et al. Calcium suppresses central angiotensin II pressor response less in SHR. Clin Exp Hypertens 1992; A14: 1017–35

    Article  CAS  Google Scholar 

  231. Cabrera C, Bohr D. The role of nitric oxide in the central control of blood pressure. Biochem Biophys Res Commun 1995; 206(1): 77–81

    Article  PubMed  CAS  Google Scholar 

  232. Broten TP, Miyashiro JK, Moncada S, et al. Role of endothelium-derived relaxing factor in parasympathetic coronary vasodilation. Am J Physiol 1992; 262: H1579–84

    PubMed  CAS  Google Scholar 

  233. Loke KE, Sobey CG, Dusting GJ, et al. Cholinergic neurogenic vasodilatation is mediated by nitric oxide in the dog hindlimb. Cardiovasc Res 1994; 28: 542–7

    Article  PubMed  CAS  Google Scholar 

  234. Kitagawa H, Takeda F, Kohei H. Endothelium-dependent increases in rat gastric mucosal hemodynamics induced by acetylcholine and vagal stimulation. Eur J Pharmacol 1987; 133: 57–63

    Article  PubMed  CAS  Google Scholar 

  235. Van Riper DA, Bevan JA. Electrical field stimulation-mediated relaxation of rabbit middle cerebral artery: evidence of a cholinergic endothelium-dependent component. Circ Res 1992; 70: 1104–12

    Article  PubMed  Google Scholar 

  236. Pierzga JM, Segal SS. Spatial relationships between neuromuscular junctions and microvessels in hamster cremaster muscle. Microvasc Res 1994; 48: 50–67

    Article  PubMed  CAS  Google Scholar 

  237. Segal SS. Invited editorial on ‘Nitric oxide release is present from incubated skeletal muscle preparations’. J Appl Physiol 1994; 77(6): 2517–8

    PubMed  CAS  Google Scholar 

  238. Granger DL, Lehninger AL. Site of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells. J Cell Biol 1982; 95: 527–35

    Article  PubMed  CAS  Google Scholar 

  239. Drapier SR, Hibbs JB. Murine cytotoxic activated macrophages inhibit aconitase in tumor cells. J Clin Invest 1986; 78: 790–7

    Article  PubMed  CAS  Google Scholar 

  240. Drapier SC, Hibbs JB. Differentiation of murine macrophages lo express nonspecific cytotoxicity for tumor results in L-arginine-dependent inhibition of mitochondrial iron-sulphur enzymes in the macrophage effector cells. J Immunol 1988; 140: 2829–38

    PubMed  CAS  Google Scholar 

  241. Shen W, Xu X, Ochoa M, et al. Role of nitric oxide in the regulation of oxygen consumption in conscious dogs. CircRes 1994; 75: 1086–95

    CAS  Google Scholar 

  242. King CE, Melinyshyn MJ, Mewburn JD, et al. Canine hindlimb blood flow and O2 uptake after inhibition of EDRF/NO synthesis. J Appl Physiol 1994; 76(3): 1166–71

    PubMed  CAS  Google Scholar 

  243. Murrant CL, Woodley NE, Barclay JK. Effect of nitroprusside and endothelium-derived products on slow-twitch skeletal muscle function in vitro. Can J Physiol Pharmacol 1994; 72: 1089–93

    Article  PubMed  CAS  Google Scholar 

  244. Balon TW, Nadler JL. Nitric oxide release is present from incubated skeletal muscle preparations. J Appl Physiol 1994; 77(6): 2519–21

    PubMed  CAS  Google Scholar 

  245. Gillespie JS, Liu X, Martin W. The effects of L-arginine and NG-monomethyl-L-arginine on the response of the rat an-ococcygeus to NANC nerve stimulation. Br J Pharmacol 1989; 98: 1080–2

    Article  PubMed  CAS  Google Scholar 

  246. Li CG, Rand MJ. Evidence that part of the NANC relaxant response of guinea-pig trachea to electrical field stimulation is mediated by nitric oxide. Br J Pharmacol 1991; 102: 91–4

    Article  PubMed  CAS  Google Scholar 

  247. Bult H, Bocckxstaens GE, Pelckmans PA, et al. Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature (Lond) 1990; 345: 346–7

    Article  CAS  Google Scholar 

  248. Falcone JC, Bohlen HG. EDRF from rat intestine and skeletal muscle venules causes dilation of arterioles. Am J Physiol 1990; 258: H1515–23

    PubMed  CAS  Google Scholar 

  249. Baez S. Skeletal muscle and gastrointestinal microvascular morphology. In: Kaley G, Altura BM, editors. Microcirculation. Baltimore (MD): University Park Press, 1977: 69–94

    Google Scholar 

  250. Lash JM, Bohlen HG. Perivascular and tissue PO2 in contracting rat spinotrapezius muscle. Am J Physiol 1987; 252: HI 192–202

    Google Scholar 

  251. Saito Y, Eraslan A, Lackard V, et al. Role of venular endothelium in control of arteriolar diameter during functional hyperae-mia. Am J Physiol 1994; 267: H1227–31

    PubMed  CAS  Google Scholar 

  252. Hester RL, During BR. Red cell velocity during functional hyperaemia: implications for rheology and oxygen saturation. Am J Physiol 1988; 255: H236–44

    PubMed  CAS  Google Scholar 

  253. Laughlin MH. Skeletal muscle blood flow capacity: role of muscle pump in exercise hyperaemia. Am J Physiol 1987; 253:H993–1004

    PubMed  CAS  Google Scholar 

  254. Melkumyants AM, Balashov SA, Klimachev AN, et al. Nitricoxide does not mediate flow induced endothelium dependent arterial dilatation in the cat. Cardiovasc Res 1992; 26: 256–60

    Article  PubMed  CAS  Google Scholar 

  255. Koller A, Kaley G. Prostaglandins mediate arteriolar dilation to increased blood flow velocity in skeletal muscle microcirculation. Cire Res 1990; 67: 529–34

    Article  CAS  Google Scholar 

  256. Koller A, Sun D, Kaley G. Role of shear stress and endothelial prostaglandins in flow and viscosity-induced dilation of arterioles in vitro. Circ Res 1993; 72: 1276–84

    Article  PubMed  CAS  Google Scholar 

  257. Janczewska H, Herbaczynska-Cedro K. Effect of indomethacin on vascular responses to vasoactive agents in working muscle in the dog. Pol J Pharmacol Pharm 1974; 26: 159–66

    PubMed  CAS  Google Scholar 

  258. Herbaczynska-Cedro K, Staszewska-Barczak J, Janczewska H. Muscular work and the release of prostaglandin-like substances. Cardiovasc Res 1976; 10: 413–20

    Article  PubMed  CAS  Google Scholar 

  259. Quadt JFA, Voss R, TenHoor T. Prostacyclin production of the isolated pulsatingly perfused rat aorta. J Pharmacol Methods 1982; 7: 263–70

    Article  PubMed  CAS  Google Scholar 

  260. Frangos JA, Eskin SG, McIntyre LW, et al. Flow effects on prostacyclin production by cultured human endothelial cells. Science 1985; 227: 1477–9

    Article  PubMed  CAS  Google Scholar 

  261. Szwajktyn K, Lamping KG, Dole WP Role of endothelium-derived relaxing factor and prostaglandins in responses of coronary arteries to thromboxane in vivo. Circ Res 1990; 66: 1729–37

    Article  Google Scholar 

  262. Kilblom A, Wennmalm A. Endogenous prostaglandins as local regulators of blood flow in man: effect of indomethacin on reactive and functional hyperaemia. J Physiol (Lond) 1976; 257: 109–21

    Google Scholar 

  263. Staessen J, Cattaert A, Fagard R, et al. Hemodynamic and humoral effects of prostaglandin inhibition in exercising humans. J Appl Physiol 1984; 56: 39–45

    PubMed  CAS  Google Scholar 

  264. Cowley AJ, Stainer K, Rowley JM, et al. Effect of aspirin and indomethacin on exercise-induced changes in blood pressure and limb blood flow in normal volunteers. Cardiovasc Res 1985; 19: 177–80

    Article  PubMed  CAS  Google Scholar 

  265. Vallance P, Patton S, Bhagat K, et al. Direct measurement of nitric oxide in human beings. Lancet 1995; 345: 153–4

    Article  Google Scholar 

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  1. Department of Human Movement, The University of Western Australia, Nedlands, Western Australia, 6009, Australia

    Daniel J. Green & Brian A. Blanksby

  2. Department of Medicine and Cardiology, The University of Western Australia, Nedlands, Western Australia, Australia

    Gerry O’Driscoll & Roger R. Taylor

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Green, D.J., O’Driscoll, G., Blanksby, B.A. et al. Control of Skeletal Muscle Blood Flow During Dynamic Exercise. Sports Med 21, 119–146 (1996). https://doi.org/10.2165/00007256-199621020-00004

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