Contribution of Endogenous Catecholamines to Preconditioning: Is it through Facilitation of Adenosine Production?

  • Katsuo Suzuki
  • Akihito Tsuchida
  • Tetsuji Miura
Part of the Progress in Experimental Cardiology book series (PREC, volume 1)


Studies using adrenoceptor blockers have reponed very contradictory results and do not allow us to draw a clear conclusion about the role of adrenoceptors in infarct size limitation by preconditioning. However, reserpinization consistently abolished the protection of preconditioning in our studies and in those of others, indicating the contribution of endogenous catecholamines. Our findings using microdialysis suggest that the role of catecholamines in preconditioning is not through modulating production of adenosine, a key trigger of the preconditioning mechanism. In light of the negative data from adrenoceptor blockers on preconditioning the rabbit, it is speculated that the contribution of endogenous catecholamines, at least in this species, may be through a non-receptor-mediated mechanism such as free radicals.


Infarct Size Adenosine Receptor Ischemic Precondition Coronary Occlusion Adrenoceptor Blocker 
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.
    Downey JM, Miura T. 1994. The role of adenosine in ischemic preconditioning. In Hoti M, Maruyama M, Reneman RS (eds), Cardiac Adaptation and Failure. Tokyo: Springer-Verlag, pp. 147–166.Google Scholar
  2. 2.
    Wall TM, Sheely R, Harmtman JC. 1994. Role of bradykinin in myocardial preconditioning. J Pharmacol Exp Ther 270:681–689.PubMedGoogle Scholar
  3. 3.
    Goto M, Liu Y, Yang XM, Ardell JL, Cohen MV, Downey JM. 1995. Role of bradykinin in protection of ischemic preconditioning in rabbit hearts. Circ Res 77:611–621.PubMedGoogle Scholar
  4. 4.
    Chien GL, Van Winkle DM. 1996. Naloxone blockade of myocardial ischemic preconditioning is stereoselective. J Mol Cell Cardiol 28:1895–1900.PubMedCrossRefGoogle Scholar
  5. 5.
    Miki T, Sato H, Cohen MV, Downey JM. 1996, Opioid receptor contributes to ischemic preconditioning through protein kinase C activation in rabbits (abstract). Circulation 94(Suppl I):1392–1393.Google Scholar
  6. 6.
    Olsson RA, Pearson JD. 1991. Cardiopurinoceptors. Physiol Rev 70:761–845.Google Scholar
  7. 7.
    Mubagwa K, Mullane K, Flameng W. 1996. Role of adenosine in the heart and circulation. Cardiovasc Res 32:797–813.PubMedCrossRefGoogle Scholar
  8. 8.
    Liu GS, Richards GS, Olsson RA, Mullane K, Walsh RS, Downey JM. 1994. Evidence that the adenosine A3 receptor may mediate the protection afforded by preconditioning in the isolated rabbit heart. Cardiovasc Res 28:1057–1061.PubMedGoogle Scholar
  9. 9.
    Thornton JD, Thornton CS, Downey JM. 1993. Effect of adenosine receptor blockade: preventing protective preconditioning depends on time of initiation. Am J Physiol 265:H504–H508.PubMedGoogle Scholar
  10. 10.
    Miura T, Ogawa T, Iwamoto T, Shimamoto K, Iimura O. 1992. Dipyridamole potentiates the myocardial infarct size-limiting effect of preconditioning. Circulation 86:979–985.PubMedGoogle Scholar
  11. 11.
    Malliani A, Schwartz PJ, Zanchetti A. 1969. A sympathetic reflex elicited by experimental coronary occlusion. Am J Physiol 217:703–709.PubMedGoogle Scholar
  12. 12.
    Schomig A, Haass M, Richard G. 1991. Catecholamine release and arrhythmias in acute myocardial ischemia. Eur Heart J 12(Suppl F):38–47.PubMedGoogle Scholar
  13. 13.
    Bunger R, Mallet RT, Hartman DA. 1998. Redox manipulation of free cardiac adenylates and purine nucleoside release. Reciprocity between cytosolic phosphorylation potential and reduction-oxidation state or free AMP in perfused working heart. In de Jong JW (ed), Myocardial Energy Metabolism. Dordrecht: Martinus Nijihoff, pp. 67–81.Google Scholar
  14. 14.
    Deussen A, Schrader J. 1991. Cardiac adenosine production is linked to myocardial PO2. J Mol Cell Cardiol 23:495–504.PubMedCrossRefGoogle Scholar
  15. 15.
    Fenton RA, Dobson JG Jr. 1993. Hypoxia enhances isoproterenol-induced increase in heart interstitial adenosine, depressing β-adrenergic contractile responses. Circ Res 72:571–578.PubMedGoogle Scholar
  16. 16.
    Kitakaze M, Hori M, Tamai J, et al. 1987. α1-Adrenoceptor activity regulates release of adenosine from the ischemic myocardium in dogs. Circ Res 60:631–639.PubMedGoogle Scholar
  17. 17.
    Kitakaze M, Hori M, Morioka T, et al. 1994. α1-Adrenoceptor activation mediates the infarct size-limiting effect of ischemic preconditioning through augmentation of 5′-nucleotidase activity. J Clin Invest 93:2197–2205.PubMedGoogle Scholar
  18. 18.
    Thornton JD, Daly JF, Cohen MV, Yang X-G, Downey JM, 1993. Catecholamines can induce adenosine receptor-mediated protection of the myacardium but do not participate in ischemic preconditioning in the rabbit. Circ Res 73:649–655.PubMedGoogle Scholar
  19. 19.
    Bugge E, Ytrehus K. 1995. Ischaemic preconditioning is protein kinase C dependent but not through stimulation of alpha adrenergic or adenosine receptors in the isolated rat heart. Cardiovasc Res 29:401–406.PubMedCrossRefGoogle Scholar
  20. 20.
    Van Winkle DM, Haessler R, Wolff RA, Kuzume K, Anselone CG, Davis RF. 1994. α-Adrenergic cardioprotection involves adenosine, but ischemic preconditioning does not involve α-adrenergic activation (abstract). FASEB J 8:A569.Google Scholar
  21. 21.
    Tsuchida A, Miura T, Miki T, Sakamoto J, Iimura O. 1994. Role of α1-adrenergic receptor and protein kinase C in infarct size limitation by ischemic preconditioning in rat heart (abstract). Circulation 90(Suppl I):1–647.Google Scholar
  22. 22.
    Miura T, Goto M, Miki T, Sakamoto J, Shimamoto K, Iimura O. 1995. Glibenclamide, a blocker of ATP-sensitive potassium channels, abolishes infarct size limitation by preconditioning in rabbits anesthetized with xylazine/pentobarbital but not with pentobarbital alone. J Cardiovasc Phamacol 25:531–538.CrossRefGoogle Scholar
  23. 23.
    Kariya T, Minatoguchi S, Ohno T, et al. 1995. Selective α1-antagonist, Bunazosin, can dose-dependently block infarct size limiting effect of ischemic preconditioning in rabbits (abstract). J Mol Cell Cardiol 27:A519.Google Scholar
  24. 24.
    Sebbag L, Katsuragawa M, Verbinski S, Jennings RB, Reimer KA. 1993. Intracoronary administration of the α1-receptor agonist, methoxamine, does not reproduce the infarct-limiting effect of ischemic preconditioning in dogs. Cardiovasc Res 32:830–838.CrossRefGoogle Scholar
  25. 25.
    Grover GJ, Sleph PG, Czwonczyk S. 1992. Role of ATP-sensitive potassium channels in mediating preconditioning in the dog heart and their possible interaction with adenosine A1-receptors. Circulation 86:1310–1316.PubMedGoogle Scholar
  26. 26.
    Yao Z, Gross GJ. 1994. A comparison of adenosine-induced cardioprotection and ischemic preconditioning in dogs. Efficacy, time course, and role of KATP channels. Circulation 89:1229–1236.PubMedGoogle Scholar
  27. 27.
    Van Winkle DM, Chien GL, Wolff RA, Soifer BE, Kuzume K, Davis RF. 1994. Cardioprotection provided by adenosine receptor activation is abolished by blockade of the KATP channel. Am J Physiol 266:H829–H839.PubMedGoogle Scholar
  28. 28.
    Liu Y, Downey JM. 1992. Ischemic preconditioning protects against infarction in rat heart. Am J Physiol 263:H1107–H1112.PubMedGoogle Scholar
  29. 29.
    Li Y, Kloner RA. 1993. The cardioprotective effects of ischemic preconditioning are not medicated by adenosine receptors in rat hearts. Circulation 87:1642–1648.PubMedGoogle Scholar
  30. 30.
    Toombs CF, Wlitse AL, Shebuski RJ. 1993. Ischemic preconditioning fails to limit infarct size in reserpinized rabbit myocardium. Implication of norepinephrine release in the preconditioning effect. Circulation 88:2351–2358.PubMedGoogle Scholar
  31. 31.
    Thornton JD, Thornton CS, Sterling DJ, Downey JM. 1993. Blockade of ATP-sensitive potassium channels increases infarct size but does not prevent preconditioning in rabbit hearts. Circ Res 72:44–49.PubMedGoogle Scholar
  32. 32.
    Toombs CF, Moore TL, Shebuski RJ. 1993. Limitation of infarct size in the rabbit by ischaemic preconditioning is reversible with glibenclamide. Cardiovas Res 27:617–622.Google Scholar
  33. 33.
    Vander Heide RS, Schwartz LM, Jennings RB, Reimer KA, 1995. Effect of catecholamine depletion on myocardial infarct size in dogs: role of catecholamines in ischemic preconditioning. Cardiovasc Res 30:656–662.PubMedCrossRefGoogle Scholar
  34. 34.
    Ardell JL, Yang X-M, Barron RA, Downey JM, Cohen MV. 1996. Endogenous myocardial norepinephrine is not essential for ischemic preconditioning in rabbit heart. Am J Physiol 270:H1078–H1084.PubMedGoogle Scholar
  35. 35.
    Miura T, Suzuki K, Shimamoto K, Iimura O. 1996. Suppression of the degradation of adenine nucleotides during ischemia may not be sufficient mechanism for infarct size limitation by preconditioning. Basic Res Cardiol 91:452–432.CrossRefGoogle Scholar
  36. 36.
    Olah ME, Stiles GL. 1992, Adenosine receptors. Annu Rev Physiol 54:211–215.PubMedCrossRefGoogle Scholar
  37. 37.
    Tanaka M, Fujiwara H, Yamasaki K, Sasayama S. 1994. Superoxide dismutase and N2-mercaptopropionyl glycine attenuate infarct size limitation effect of ischemic preconditioning in the rabbit. Cardiovasc Res 28:980–986.PubMedCrossRefGoogle Scholar
  38. 38.
    Baines CP, Goto M, Downey JM. 1996. Oxygen free radical release during ischemic preconditioning triggers protection in rabbit myocardium via activation of protein kinase C. Circulation 94(Suppl I):1–424.Google Scholar
  39. 39.
    Tokube K, Kiyosue T, Arita M. 1996. Opening of cardiac KATP channel by oxygen free radicals produced by xanthine oxidase reaction. Am J Physiol 271:H478–H489.PubMedGoogle Scholar
  40. 40.
    Ichinari K, Kakei M, Matsuoka T, Nakashima H, Tanaka H. 1996. Direct activation of the ATP-sensitive potassium channel by oxygen free radicals in guinea-pig ventricular cells: its potentiation by MgADP. J Mol Cell Cardiol 28:1867–1877.PubMedCrossRefGoogle Scholar
  41. 41.
    Downey JM, Yellon DM. 1992. Do free radicals contribute to myocardial cell death during ischemia-reperfusion? In Yellon DM, Jennings RB, (ed), Myocardial Protection: The Pathophysiology of Reperfusion and Reperfusion Injury. New York: Raven Press, pp. 35–57.Google Scholar
  42. 42.
    Rump AFE, Rosen R, Klaus W. 1993. Cardioprotection by superoxide dismutase: A catecholamine-dependent process? Anesth Analg 76:239–246.PubMedCrossRefGoogle Scholar
  43. 43.
    Rump AFE, Klaus W. 1994. Evidence for norepinephrine cardiotoxicity mediated by superoxide anion radicals in isolated rabbit hearts. Naunyn-Schmiedebergs Arch Pharmacol 349:295–300.PubMedGoogle Scholar
  44. 44.
    Ytrehus K, Liu Y, Downey JM. 1994. Preconditioning protects ischemic rabbit heart by protein kinase C activation. Am J Physiol 266:H1145–H1152.PubMedGoogle Scholar
  45. 45.
    Speechly-Dick ME, Mocanu MM, Yellon DM. 1994, Protein kinase C. Its role in ischemic preconditioning in the rat. Circ Res 75:586–590.PubMedGoogle Scholar
  46. 46.
    Liu Y, Cohen MV, Downey JM. 1994. Chelerythrine, a highly selective protein kinase C inhibitor, blocks the anti-infarct effect of ischemic preconditioning in rabbit hearts. Cardiovasc Drugs Ther 8:881–882.PubMedCrossRefGoogle Scholar
  47. 47.
    Sakamoto J, Miura T, Goto M, Iimura O. 1995. Limitation of myocardial infarct size by adenosine A1 receptor activation is abolished by protein kinase C inhibitors in the rabbit. Cardiovasc Res 29:682–688.PubMedCrossRefGoogle Scholar
  48. 48.
    Komachi H, Yanagisawa K, Shirasaki Y, Miyatake T. 1994. Protein kinase C subspecies in hippocampus and striatum of reserpinized rat brain. Brain Res 634:127–130.PubMedCrossRefGoogle Scholar
  49. 49.
    Hilgenberg L, Yearwood S, Milstein S, Miles K. 1996. Neural influence on protein kinase C isoform expression in skeletal muscle. J Neurosci 16:4994–5003.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Katsuo Suzuki
    • 1
  • Akihito Tsuchida
    • 1
  • Tetsuji Miura
    • 1
  1. 1.Sapporo Medical University School of MedicineJapan

Personalised recommendations