Pflügers Archiv

, Volume 369, Issue 1, pp 1–6 | Cite as

Release of adenosine, inosine and hypoxanthine from the isolated guinea pig heart during hypoxia, flow-autoregulation and reactive hyperemia

  • Jürgen Schrader
  • Francis J. Haddy
  • Eckehart Gerlach


In an attempt to test the hypothesis whether adenosine is involved in the regulation of coronary flow, adenosine, inosine and hypoxanthine were measured in the effluent perfusate and in the tissue of isolated guinea pig hearts under various experimental conditions. In addition, the release of14C-adenosine,14C-inosine and14C-hypoxanthine was determined after prelabeling cardiac adenine nucleotides with14C-adenine.

The decrease in coronary resistance induced by hypoxic perfusion (30% and 20% in the gas phase) and during autoregulation was associated with a considerable increase in the release of adenosine, inosine and hypoxanthine. Under both conditions the concentrations of adenosine in the effluent perfusate were clearly within the coronary vasodilating range of exogenously administered adenosine. The tissue content of adenosine also increased significantly when the perfusion pressure was reduced. The release of14C-adenosine closely paralleled the changes in coronary resistance during hypoxic perfusion, autoregulation and during reactive hyperemia. The specific activity of adenosine in the effluent perfusate, however, decreased substantially upon reduction of the oxygen supply to the heart, indicating that the release of14C-adenosine does not provide an absolute measure of total adenosine release by the heart.

Our data indicate that the greater part of the adaptive changes of vascular resistance during hypoxia and autoregulation can be attributed to adenosine which is formed at an enhanced rate under these conditions. However, other factors might be involved as well.

Key words

14C-adenine Coronary flow Adenosine Inosine Hypoxanthine Hypoxia Autoregulation Reactive hyperemia 


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  1. 1.
    Berne, R. M.: Cardiac nucleotides in hypoxia: possible role in regulation of coronary blood flow. Amer. J. Physiol.204, 317–322 (1963)Google Scholar
  2. 2.
    Berne, R. M., Rubio, R., Duling, B. R., Wiedmeier, V. T.: Effects of acute and chronic hypoxia on coronary blood flow. Advanc. Cardiol5, 56–66 (1970)Google Scholar
  3. 3.
    Bünger, R., Haddy, F. J., Querengässer, A., Gerlach, E.: An isolated guinea pig heart preparation with in vivo like features. Pflügers Arch.353, 317–326 (1975)Google Scholar
  4. 4.
    Gerlach, E., Deuticke, B., Dreisbach, R. H.: Der Nucleotid-Abbau im Herzmuskel bei Sauerstoffmangel und seine mögliche Bedeutung für die Coronardurchblutung. Naturwissenschaften50, 228–229 (1963)Google Scholar
  5. 5.
    Granger, H. J., Shepherd, A. P.: Intrinsic microvascular control of tissue oxygen delivery. Microvasc. Res.5, 49–72 (1973)Google Scholar
  6. 6.
    Guyton, A. C., Ross, J. M., Carrier, O., Walker, J. R.: Evidence for tissue oxygen demand as a major factor causing autoregulation. Circulat. Res. (Suppl. I)14, 60–80 (1964)Google Scholar
  7. 7.
    Haddy, F. J., Scott, J. B.: Metabolically linked chemicals in local regulation of blood flow. Physiol. Rev.48, 688–707 (1968)Google Scholar
  8. 8.
    Haddy, F. J., Scott, J. B.: Metabolic factors in peripheral circulatory regulation. Fed. Proc.34, 2004–2011 (1975)Google Scholar
  9. 9.
    Johnson, P. C.: Review of previous studies and current theories of autoregulation. Circulat. Res. (Suppl. I)14, 1–9 (1964)Google Scholar
  10. 10.
    Katory, M., Berne, R. M.: Release of adenosine from anoxic hearts. Circulat. Res.19, 420–425 (1966)Google Scholar
  11. 11.
    Mosher, P., Ross, J., McFate, P. A., Shaw, R. F.: Control of coronary blood flow by an autoregulatory mechanism. Circulat. Res.14, 250–259 (1964)Google Scholar
  12. 12.
    Olsson, R. A.: Changes in content of purine nucleosides in canine myocardium during coronary occlusion. Circulat. Res.26, 301–306 (1970)Google Scholar
  13. 13.
    Olsson, R. A.: Myocardial reactive hyperemia. Circulat. Res.37, 263–270 (1975)Google Scholar
  14. 14.
    Rubio, R., Berne, R. M.: Release of adenosine by the normal myocardium in dogs and its relation to the regulation of coronary resistance. Circulat. Res.25, 407–415 (1969)Google Scholar
  15. 15.
    Rubio, R., Berne, R. M., Katori, M.: Release of adenosine in reactive hyperemia of the dog heart. Amer. J. Physiol.216, 56–62 (1969)Google Scholar
  16. 16.
    Rubio, R., Wiedemeier, V. T., Berne, R. M.: Nucleoside-phosphorylase: localisation and role in the myocardial distribution of purines. Amer. J. Physiol.122, 550–555 (1972)Google Scholar
  17. 17.
    Rubio, R., Wiedmeier, V. T., Berne, R. M.: Relationship between coronary flow and adenosine production and release. J. Molec. Cell. Cardiol.6, 561–566 (1974)Google Scholar
  18. 18.
    Schrader, J., Gerlach, E.: Compartmentation of cardiac adenine nucleotides and formation of adenosine. Pflügers Arch.367, 129–135 (1976)Google Scholar
  19. 19.
    Snow, J. A., Olsson, R. A., Gentry, M. K.: Myocardial: blood purine nucleoside concentration ratios in canine myocardium. In: Current topics in coronary research (C. M. Bloor and R. A. Olsson, eds.). New York-London: Plenum Press 1973Google Scholar
  20. 20.
    Wiedmeier, V. T., Rubio, R., Berne, R. M.: Incorporation and turnover of adenosine-U-14C in perfused guinea pig myocardium. Amer. J. Physiol.223, 51–54 (1972)Google Scholar

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • Jürgen Schrader
    • 1
  • Francis J. Haddy
    • 1
  • Eckehart Gerlach
    • 1
  1. 1.Physiologisches Institut der Universität MünchenMünchen 2Federal Republic of Germany

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