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Hypoxia pp 349-363 | Cite as

Roles of adenosine and nitric oxide in skeletal muscle in acute and chronic hypoxia

  • Janice M. Marshall
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 502)

Abstract

In experiments on anaesthetised rats, the roles played by adenosine and nitric oxide (NO) were determined in resting skeletal muscle in acute systemic hypoxia and during acclimation to chronic systemic hypoxia. It is concluded that adenosine acting on A1 receptors, at least in part in an NO-dependent manner, plays essential roles in causing the dilation of proximal and terminal arterioles that helps to maintain muscle O2 consumption when O2 delivery is reduced by acute systemic hypoxia. It is proposed that adenosine and NO are similarly responsible for causing the tonic vasodilation that gradually wanes in the first 7 days of chronic hypoxia and that concomitantly, adenosine and hypoxia stimulate VEGF expression, so increasing venular permeability and triggering angiogenesis. By 7 days of chronic hypoxia, arteriolar remodelling is well established and within 18–21 days, substantial capillary angiogenesis alleviates tissue hypoxia. At this time, vasoconstrictor responses to the sympathetic transmitter norepinephrine are reduced, but dilator responses to adenosine released by acute hypoxia are enhanced, as may be explained by increased sensitivity to NO. Thus, preservation of tissue oxygenation is apparently associated with impaired ability to regulate arterial pressure and vulnerability to further hypoxia.

Keywords

high altitude sympathetic activity oxygen consumption vasodilation endothelium angiogenesis vascular permeability 

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References

  1. 1.
    Abbas MR, and Marshall JM. The role of prostaglandins in skeletal muscle vasodilatation evoked by acute systemic hypoxia in the rat. J Physiol 523P: 248–249P, 2000.Google Scholar
  2. 2.
    Adair TH, Gay WJ, and Montani JP. Growth regulation of the vascular system: evidence for a metabolic hypothesis. Am J Physiol 259: R393–R404, 1990.PubMedGoogle Scholar
  3. 3.
    Bartlett IS, and Marshall JM. Comparison of the effects of acute hypoxia on iliac artery rings from normal and chronically hypoxic rats. Br J Pharmacol 116: 203P, 1995.Google Scholar
  4. 4.
    Bartlett IS, and Marshall JM. Mechanisms underlying the depression of noradrenaline-evoked contractions induced by chronic hypoxia in the rat iliac artery in vitro. J Physiol 491P: P24–P25, 1996.Google Scholar
  5. 5.
    Breen EC, Johnson EC, Wagner H, Tseng H-M, Sung LA, and Wagner PD. Angiogenic growth factor mRNA responses in muscle to a single bout of exercise. J Appl Physiol 81:355–361, 1996.PubMedGoogle Scholar
  6. 6.
    Bryan PT, and Marshall JM. Adenosine receptor subtypes and vasodilatation in rat skeletal muscle during systemic hypoxia: A role for A1 receptors. J Physiol 514: 151–162, 1999.PubMedCrossRefGoogle Scholar
  7. 7.
    Bryan PT, and Marshall JM. Cellular mechanisms by which adenosine induces vasodilatation in rat skeletal muscle: Significance for systemic hypoxia. J Physiol 514: 163–175, 1999.PubMedCrossRefGoogle Scholar
  8. 8.
    Dart C, and Standen N. Adenosine activated potassium current in smooth muscles isolated from pig coronary artery. J Physiol 471: 767–786, 1993.PubMedGoogle Scholar
  9. 9.
    Deussen A, Moser G, and Schrader J. Contribution of endothelial cells to cardiac adenosine production. Pflugers Arch 406: 608–614, 1986.PubMedCrossRefGoogle Scholar
  10. 10.
    Deveci D, Marshall JM, and Egginton SE. The relationship between capillary angiogenesis, muscle activity, fibre type and fibre size in chronic systemic hypoxia. Am J Physiol. In Press.Google Scholar
  11. 11.
    Doyle MP, and Walker BR. Alteration of systemic vasoreactivity in chronically hypoxic rats. Am J Physiol 260: R1114–R1122, 1991.PubMedGoogle Scholar
  12. 12.
    Edmunds NJ, and Marshall JM. Vasodilatation, oxygen delivery and oxygen consumption in rat hindlimb during systemic hypoxia: roles of nitric oxide. J Physiol 532: 251–259, 2001.PubMedCrossRefGoogle Scholar
  13. 13.
    Edmunds NJ, and Marshall JM. Oxygen delivery and oxygen consumption in rat hindlimb during systemic hypoxia: role of adenosine. J Physiol. In Press.Google Scholar
  14. 14.
    Fischer S, Knoll R, Renz D, Karliczek GF, and Schaper W. Role of adenosine in the hypoxic induction of vascular endothelial growth factor in porcine brain derived microvascular endothelial. Cells Endothel 5: 155–165, 1997.CrossRefGoogle Scholar
  15. 15.
    Harrison DK, Kessler M, and Knauff SK. Regulation of capillary blood flow and oxygen supply in skeletal muscle in dogs during hypoxaemia. J Physiol 420: 431–446, 1990.PubMedGoogle Scholar
  16. 16.
    Heath D, and Williams DR. Man at High Altitude. Churchill Livingstone, 1977.Google Scholar
  17. 17.
    Heistad DD, Abboud FM, Mark AL, and Schmidt PG. Impaired reflex vasoconstriction in chronically hypoxemic patients. J Clin Invest 51: 331–337, 1972.PubMedCrossRefGoogle Scholar
  18. 18.
    Leuenberger UA, Gray K, and Herr MD. Adenosine contributes to hypoxia-induced vasodilation in humans. J Appl Physiol 87: 2218–2224, 1999.PubMedGoogle Scholar
  19. 19.
    Marshall JM. Skeletal muscle vasculature and hypoxia. NIPS 10: 274–280, 1995.Google Scholar
  20. 20.
    Marshall JM. Circulatory hypoxia In: Update in Intensive Care and Emergency Medicine. Ed: Vincent J-L. Vol 33 (Tissue Oxygenation in Acute Medicine. Ed: Sibbald WJ, Messmer K, Fink MP). Springer-Verlag, 1998.Google Scholar
  21. 21.
    Marshall JM. Adenosine and muscle vasodilatation in acute systemic hypoxia. Acta Physiol Scand 168: 561–573, 2000.PubMedCrossRefGoogle Scholar
  22. 22.
    Marshall JM, and Metcalfe JD. Analysis of the cardiovascular changes induced in the rat by graded levels of systemic hypoxia. J Physiol 407: 385–403, 1988.PubMedGoogle Scholar
  23. 23.
    Mian R, and Marshall JM. The role of adenosine in dilator responses induced in arterioles and venules of rat skeletal muscle in systemic hypoxia. J Physiol 443: 499–511, 1991c.PubMedGoogle Scholar
  24. 24.
    Mian R, and Marshall JM. Effects of chronic hypoxia on microcirculatory responses evoked by noradrenaline. Int J Microcirc: Clin & Exp. 14: 244, 1994.Google Scholar
  25. 25.
    Mian R, and Marshall JM. The behaviour of muscle microcirculation in chronically hypoxic rats: the role of adenosine. J Physiol 491:489–498, 1996.PubMedGoogle Scholar
  26. 26.
    Minchenko A, Bauer T, Salceda S, and Caro J. Hypoxic stimulation of vascular endothelial growth factor expression in vitro and in vivo. Lab. Investigl 71: 374–379, 1994.Google Scholar
  27. 27.
    Nase GP, and Boegehold MA. Endothelium-derived nitric oxide limits sympathetic neurogenic constriction in intestinal microcirculation. Am J Physiol 273: H426–H433.Google Scholar
  28. 28.
    Price RJ, and Skalak TC. Arteriolar remodelling in skeletal muscle of rats exposed to chronic hypoxia. J Vasc Res 35: 238–244, 1998.PubMedCrossRefGoogle Scholar
  29. 29.
    Ray C, and Marshall JM. Interactions of adenosine, nitric oxide and the cyclo-oxygenase pathway in freshly excised rat aorta. J Physiol 528P: 111P, 2000.Google Scholar
  30. 30.
    Sirois MG, and Edelman ER. VEGF effect on vascular permeability is mediated by synthesis of platelet activating factor. Am J Physiol 272: H2746–H2756, 1997.PubMedGoogle Scholar
  31. 31.
    Skinner MR, and Marshall JM. Studies on the roles of ATP, adenosine and nitric oxide in mediating muscle vasodilatation induced in the rat by acute systemic hypoxia. J Physiol 495: 553–560, 1996.PubMedGoogle Scholar
  32. 32.
    Smith K, and Marshall JM. Physiological adjustments and arteriol remodelling within skeletal muscle during acclimation to chronic hypoxia in the rat. J Physiol 521: 261–272, 1999.PubMedCrossRefGoogle Scholar
  33. 33.
    Thomas T, Elnazir BK, and Marshall JM. Differentiation of the peripherally-mediated from the centrally-mediated influences of adenosine in the rat during systemic hypoxia. Exp Physiol 79: 809–822, 1994.PubMedGoogle Scholar
  34. 34.
    Thomas T, and Marshall JM. The roles of adenosine in regulating the respiratory and cardiovascular systems in chronically hypoxic, adult rats. J Physiol 501: 439–447, 1997.PubMedCrossRefGoogle Scholar
  35. 35.
    Walsh MP, and Marshall JM. Early effects of chronic systemic hypoxia upon muscle circulation of the rat. J Physiol 515P: 144P, 1999.Google Scholar
  36. 36.
    Walsh M, and Marashall JM. The contribution of adenosine and A1 receptors to tonic vasodilatation in rat hindlimb muscle during early chronic systemic hypoxia. Drug Dev Res 50: 197,2000.Google Scholar
  37. 37.
    Walsh M, and Marshall JM. The roles of nitric oxide and platelet activating factor in the increase in plasma albumen extravasation evoked in skeletal muscle of the anaesthetised rat by vascular endothelial growth factor. J Physiol 525P: 14P, 2000.Google Scholar
  38. 38.
    Walsh M, and Marshall JM. Early effects of chronic systemic hypoxia upon plasma extravasation in skeletal muscle of the rat: a role for vascular endothelial growth factor? J Physiol 523P: 146P, 2000.Google Scholar
  39. 39.
    Westendorp RG, Blauw GJ, Frolich M, and Simons R. Hypoxic syncope. Aviation Space & Environmental Medicine 68(5): 410–414, 1997.Google Scholar
  40. 40.
    Wu HM, Huang O, Yuan Y, and Granger HJ. VEGF induces NO-dependent hyperpermeability in coronary venules. Am J Physiol 271: H2735–H2739, 1996.PubMedGoogle Scholar
  41. 41.
    Xu F, and Severinghaus JW. Rat brain VEGF expression in alveolar hypoxia: possible role in high altitude. J Appl Physiol 85: 53–57, 1998.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Janice M. Marshall
    • 1
  1. 1.Department of PhysiologyThe Medical SchoolBirminghamUK

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