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Metabolic coronary flow regulation—Current concepts

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Abstract

The concept of metabolic coronary flow control provides a rationale for the close relationship of coronary flow and myocardial metabolic rate of oxygen. The concept is based on the presence of an oxygen (metabolic) sensor coupled functionally to effector mechanisms, which control vascular tone. Four modes of metabolic control models have been proposed. 1) An oxygen sensor located in the wall of coronary vessels coupling to smooth muscle tension. Endothelial prostaglandin production may support this concept. 2) An oxygen sensing mechanism located in the myocardium and changing metabolism in response to changes of local pO2. Adenosine is a metabolite produced at an accelerated rate when the supply-to-demand relationship for oxygen falls. 3) Sensing of oxygen turnover may be achieved by carbon dioxide production and, potentially, by mitochondrial production of reactive oxygen species. 4) The red blood cell might serve as an oxygen sensor in response to changes of haemoglobin oxygenation. A potential link to vessel relaxation may be red cell ATP release. A large body of experimental evidence supports the notion that KATP channels play a significant role causing smooth muscle hyperpolarisation. However, additional yet unknown effector mechanisms must exist, because block of KATP channels does not lead to deterioration of coronary flow control under conditions of exercise. Thus, although several lines of evidence show that metabolic flow regulation is effective during hypoxic conditions,mechanisms mediating normoxic metabolic flow control still await further clarification.

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References

  1. Akatsuka Y, Egashira K, Katsuda Y, Narishige T, Ueno H, Shimokawa H, Takeshita A (1994) ATP sensitive potassium channels are involved in adenosine A2 receptor mediated coronary vasodilatation in the dog. Cardiovasc Res 28:906–911

    PubMed  CAS  Google Scholar 

  2. Aley PK, Porter KE, Boyle JP, Kemp PJ, Peers C (2005) Hypoxic modulation of Ca2+ signaling in human venous endothelial cells. Multiple roles for reactive oxygen species. J Biol Chem 280:13349–13354

    Article  PubMed  CAS  Google Scholar 

  3. Aversano T, Ouyang P, Silverman H, Ziegelstein RC, Gips S (1993) Effect of blockade of the ATP-sensitive potassium channel on metabolic coronary vasodilation in the dog. Pharmacology 47:360–368

    PubMed  CAS  Google Scholar 

  4. Bak MI, Ingwall JS (1994) Acidosis during ischemia promotes adenosine triphosphate resynthesis in postischemic rat heart. In vivo regulation of 5’-nucleotidase. J Clin Invest 93:40–49

    PubMed  CAS  Google Scholar 

  5. Bak MI, Ingwall JS (1998) Regulation of cardiac AMP-specific 5’-nucleotidase during ischemia mediates ATP resynthesis on reflow. Am J Physiol 274:C992–C1001

    PubMed  CAS  Google Scholar 

  6. Bardenheuer H, Schrader J (1983) Relationship between myocardial oxygen consumption, coronary flow, and adenosine release in an improved isolated working heart preparation of guinea pigs. Circ Res 52:263–271

    PubMed  CAS  Google Scholar 

  7. Bouchard JF, Dumont E, Lamontagne D (1994) Evidence that prostaglandins I2, E2, and D2 may activate ATP sensitive potassium channels in the isolated rat heart. Cardiovasc Res 28:901–905

    PubMed  CAS  Google Scholar 

  8. Brand M, Deussen A (2006) Vardenafil increases coronary flow response to hypercapnic acidosis in isolated guinea pig heart (under revision)

  9. Broten TP, Feigl EO (1992) Role of myocardial oxygen and carbon dioxide in coronary autoregulation. Am J Physiol 262:H1231–H1237

    PubMed  CAS  Google Scholar 

  10. Broten TP, Romson JL, Fullerton DA, Van Winkle DM, Feigl EO (1991) Synergistic action of myocardial oxygen and carbon dioxide in controlling coronary blood flow. Circ Res 68:531–542

    PubMed  CAS  Google Scholar 

  11. Brown IP, Thompson CI, Belloni FL (1993) Role of nitric oxide in hypoxic coronary vasodilatation in isolated perfused guinea pig heart. Am J Physiol 264:H821–H829

    PubMed  CAS  Google Scholar 

  12. Busse R, Forstermann U, Matsuda H, Pohl U (1984) The role of prostaglandins in the endothelium-mediated vasodilatory response to hypoxia. Pflugers Arch 401:77–83

    Article  PubMed  CAS  Google Scholar 

  13. Dai XZ, Bache RJ (1984) Effect of indomethacin on coronary blood flow during graded treadmill exercise in the dog. Am J Physiol 247:H452–H458

    PubMed  CAS  Google Scholar 

  14. Daut J, Maier-Rudolph W, von Beckerath N, Mehrke G, Gunther K, Goedel-Meinen L (1990) Hypoxic dilation of coronary arteries is mediated by ATPsensitive potassium channels. Science 247:1341–1344

    Article  PubMed  CAS  Google Scholar 

  15. Deussen A, Borst M, Kroll K, Schrader J (1988) Formation of S-adenosylhomocysteine in the heart. II: A sensitive index for regional myocardial underperfusion. Circ Res 63:250–261

    PubMed  CAS  Google Scholar 

  16. Deussen A, Borst M, Schrader J (1988) Formation of S-adenosylhomocysteine in the heart. I: An index of free intracellular adenosine. Circ Res 63:240–249

    PubMed  CAS  Google Scholar 

  17. Deussen A, Lauer T, Loncar R, Kropp J (2001) Heterogeneity of metabolic parameters in the left ventricular myocardium and its relation to local blood flow. Basic Res Cardiol 96:564–574

    Article  PubMed  CAS  Google Scholar 

  18. Deussen A, Loncar R (1998) Metabolic aspects of myocardial ischemia. Z Kardiol 87(Suppl 2):37–40

    PubMed  Google Scholar 

  19. Deussen A, Moser G, Schrader J (1986) Contribution of coronary endothelial cells to cardiac adenosine production. Pflugers Arch 406:608–614

    Article  PubMed  CAS  Google Scholar 

  20. Deussen A, Walter C, Borst M, Schrader J (1991) Transmural gradient of adenosine in canine heart during functional hyperemia. Am J Physiol 260:H671–H680

    PubMed  CAS  Google Scholar 

  21. Dietrich HH, Ellsworth ML, Sprague RS, Dacey RG, Jr. (2000) Red blood cell regulation of microvascular tone through adenosine triphosphate. Am J Physiol Heart Circ Physiol 278: H1294–H1298

    PubMed  CAS  Google Scholar 

  22. Döring HJ, Kammermeier H (1964) Änderungen des Herzquerdurchmessers unter dem Einfluß von Sauerstoffmangel, Stoffwechsel-Inhibitoren und erregungshemmenden Substanzen. In: Fleckenstein A (ed) Kreislaufmessungen, 4. Freiburger Colloquium, E Banaschewski (publ.) München-Gräfelfing, pp 45–56

  23. Duncker DJ, Laxson DD, Lindstrom P, Bache RJ (1993) Endogenous adenosine and coronary vasoconstriction in hypoperfused myocardium during exercise. Cardiovasc Res 27:1592–1597

    PubMed  CAS  Google Scholar 

  24. Duncker DJ, Stubenitsky R, Verdouw PD (1998) Autonomic control of vasomotion in the porcine coronary circulation during treadmill exercise. Evidence for feed-forward â-adrenergic control. Circ Res 82:1312–1322

    PubMed  CAS  Google Scholar 

  25. Duncker DJ, Stubenitsky R, Verdouw PD (1998) Role of adenosine in the regulation of coronary blood flow in swine at rest and during treadmill exercise. Am J Physiol 275:H1663–H1672

    PubMed  CAS  Google Scholar 

  26. Duncker DJ, van Zon NS, Altman JD, Pavek TJ, Bache RJ (1993) Role of K+ATP channels in coronary vasodilation during exercise. Circulation 88:1245–1253

    PubMed  CAS  Google Scholar 

  27. Duncker DJ, van Zon NS, Pavek TJ, Herrlinger SK,Bache RJ (1995) Endogenous adenosine mediates coronary vasodilation during exercise after K(ATP)+ channel blockade. J Clin Invest 95:285–95

    Article  PubMed  CAS  Google Scholar 

  28. Ellsworth ML (2004) Red blood cellderived ATP as a regulator of skeletal muscle perfusion. Med Sci Sports Exerc 36:35–41

    Article  PubMed  CAS  Google Scholar 

  29. Erga KS, Seubert CN, Liang HX, Wu L, Shryock JC, Belardinelli L (2000) Role of A(2A)-adenosine receptor activation for ATP-mediated coronary vasodilation in guinea-pig isolated heart. Br J Pharmacol 130:1065–1075

    Article  PubMed  CAS  Google Scholar 

  30. Fan Z, Tokuyama Y, Makielski JC (1994) Modulation of ATP-sensitive K+ channels by internal acidification in insulinsecreting cells. Am J Physiol 267:C1036–C1044

    PubMed  CAS  Google Scholar 

  31. Farias M, III, Gorman MW, Savage MV, Feigl EO (2005) Plasma ATP during exercise: possible role in regulation of coronary blood flow. Am J Physiol Heart Circ Physiol 288:H1586–H1590

    Article  PubMed  CAS  Google Scholar 

  32. Farouque HM, Worthley SG, Meredith IT (2004) Effect of ATP-sensitive potassium channel inhibition on coronary metabolic vasodilation in humans. Arterioscler Thromb Vasc Biol 24:905–910

    Article  PubMed  CAS  Google Scholar 

  33. Farouque HM, Worthley SG, Meredith IT, Skyrme-Jones RA, Zhang MJ (2002) Effect ofATP-sensitive potassium channel inhibition on resting coronary vascular responses in humans. Circ Res 90:231–236

    Article  PubMed  CAS  Google Scholar 

  34. Feigl EO (1983) Coronary physiology. Physiol Rev 63:1–205

    PubMed  CAS  Google Scholar 

  35. Feigl EO, Neat GW, Huang AH (1990) Interrelations between coronary artery pressure, myocardial metabolism and coronary blood flow. J Mol Cell Cardiol 22:375–390

    Article  PubMed  CAS  Google Scholar 

  36. Fink B, Laude K, McCann L, Doughan A, Harrison DG, Dikalov S (2004) Detection of intracellular superoxide formation in endothelial cells and intact tissues using dihydroethidium and an HPLC-based assay. Am J Physiol Cell Physiol 287:C895–C902

    Article  PubMed  CAS  Google Scholar 

  37. Fisher MN, Newsholme EA (1984) Properties of rat heart adenosine kinase. Biochem J 221:521–528

    PubMed  CAS  Google Scholar 

  38. Frobert O, Buus CL, Rembold CM (2005) HSP20 phosphorylation and interstitial metabolites in hypoxia-induced dilation of swine coronary arteries. Acta Physiol Scand 184:37–44

    Article  PubMed  CAS  Google Scholar 

  39. Frobert O, Haink G, Simonsen U, Gravholt CH, Levin M, Deussen A (2006) Adenosine concentration in the porcine coronary artery wall and A2A receptor involvement in hypoxia-induced vasodilatation. J Physiol 570:375–384

    Article  PubMed  CAS  Google Scholar 

  40. Frobert O, Mikkelsen EO, Bagger JP, Gravholt CH (2002) Measurement of interstitial lactate during hypoxia-induced dilatation in isolated pressurised porcine coronary arteries. J Physiol 539:277–284

    Article  PubMed  CAS  Google Scholar 

  41. Ge ZD, Zhang XH, Fung PC, He GW (2000) Endothelium-dependent hyperpolarization and relaxation resistance to N(G)-nitro-L-arginine and indomethacin in coronary circulation. Cardiovasc Res 46:547–556

    Article  PubMed  CAS  Google Scholar 

  42. Gonzalez-Alonso J, Olsen DB, Saltin B (2002) Erythrocyte and the regulation of human skeletal muscle blood flow and oxygen delivery: role of circulating ATP. Circ Res 91:1046–1055

    Article  PubMed  CAS  Google Scholar 

  43. Gorlach A, Brandes RP, Bassus S, Kronemann N, Kirchmaier CM, Busse R, Schini-Kerth VB (2000) Oxidative stress and expression of p22phox are involved in the up-regulation of tissue factor in vascular smooth muscle cells in response to activated platelets. FASEB J 14:1518–1528

    Article  PubMed  CAS  Google Scholar 

  44. Groeneveld ABJ, van Beek JHGM, Alders DJC (2001) Assessing heterogeneous distribution of blood flow and metabolism in the heart. Basic Res Cardiol 96:575–581

    Article  PubMed  CAS  Google Scholar 

  45. Gurevicius J, Salem MR, Metwally AA, Silver JM, Crystal GJ (1995) Contribution of nitric oxide to coronary vasodilation during hypercapnic acidosis. Am J Physiol 268:H39–H47

    PubMed  CAS  Google Scholar 

  46. Gutterman DD, Miura H, Liu Y (2005) Redox modulation of vascular tone: focus of potassium channel mechanisms of dilation. Arterioscler Thromb Vasc Biol 25:671–678

    Article  PubMed  CAS  Google Scholar 

  47. Hattori K, Tsuchida S, Tsukahara H, Mayumi M, Tanaka T, Zhang L, Taniguchi T, Muramatsu I (2002) Augmentation of NO-mediated vasodilation in metabolic acidosis. Life Sci 71: 1439–1447

    Article  PubMed  CAS  Google Scholar 

  48. Hein TW, Belardinelli L, Kuo L (1999) Adenosine A(2A) receptors mediate coronary microvascular dilation to adenosine: role of nitric oxide and ATPsensitive potassium channels. J Pharmacol Exp Ther 291:655–664

    PubMed  CAS  Google Scholar 

  49. Hein TW, Kuo L (1999) cAMP-independent dilation of coronary arterioles to adenosine: role of nitric oxide, G proteins, and K(ATP) channels. Circ Res 85:634–642

    PubMed  CAS  Google Scholar 

  50. Heintz A, Koch T, Deussen A (2005) Intact nitric oxide production is obligatory for the sustained flow response during hypercapnic acidosis in guinea pig heart. Cardiovasc Res 66:55–63

    Article  PubMed  CAS  Google Scholar 

  51. Herrmann SC, Feigl EO (1992) Adrenergic blockade blunts adenosine concentration and coronary vasodilation during hypoxia. Circ Res 70:1203–1216

    PubMed  CAS  Google Scholar 

  52. Heusch G, Schulz R (2001) Perfusioncontraction match and mismatch. Basic Res Cardiol 96:1–10

    Article  PubMed  CAS  Google Scholar 

  53. Hinschen AK, Rose’Meyer RB, Headrick JP (2003) Adenosine receptor subtypes mediating coronary vasodilation in rat hearts. J Cardiovasc Pharmacol 41:73–80

    Article  PubMed  CAS  Google Scholar 

  54. Ikeda U, Kurosaki K, Ohya K, Shimada K (1997) Adenosine stimulates nitric oxide synthesis in vascular smooth muscle cells. Cardiovasc Res 35:168–174

    Article  PubMed  CAS  Google Scholar 

  55. Ikeda U, Kurosaki K, Shimpo M, Okada K, Saito T, Shimada K (1997) Adenosine stimulates nitric oxide synthesis in rat cardiac myocytes. Am J Physiol 273:H59–H65

    PubMed  CAS  Google Scholar 

  56. Ishibashi Y, Duncker DJ, Zhang J, Bache RJ (1998) ATP-Sensitive K+ channels, adenosine, and nitric oxide-mediated mechanisms account for coronary vasodilation during exercise. Circ Res 82:346–359

    PubMed  CAS  Google Scholar 

  57. Ishizaka H, Gudi SR, Frangos JA, Kuo L (1999) Coronary arteriolar dilation to acidosis: role of ATP-sensitive potassium channels and pertussis toxinsensitive G proteins. Circulation 99:558–563

    PubMed  CAS  Google Scholar 

  58. Ishizaka H, Kuo L (1996) Acidosis-induced coronary arteriolar dilation is mediated by ATP-sensitive potassium channels in vascular smooth muscle. Circ Res 78:50–57

    PubMed  CAS  Google Scholar 

  59. Jackson WF, Konig A, Dambacher T, Busse R (1993) Prostacyclin-induced vasodilation in rabbit heart is mediated by ATP-sensitive potassium channels. Am J Physiol 264:H238–H243

    PubMed  CAS  Google Scholar 

  60. Jensen FB (2004) Red blood cell pH, the Bohr Effect, and other oxygenationlinked phenomena in blood O2 and CO2 transport. Acta Physiol Scand 182:215–227

    Article  PubMed  CAS  Google Scholar 

  61. Juranek I, Bauer V, Donnerer J, Lembeck F, Peskar BA (2002) Severe hypoxia inhibits prostaglandin I(2) biosynthesis and vasodilatory responses induced by ionophore A23187 in the isolated rabbit ear. Pharmacology 66:199–205

    Article  PubMed  CAS  Google Scholar 

  62. Kalsner S (1977) The effect of hypoxia on prostaglandin output and on tone in isolated coronary arteries. Can J Physiol Pharmacol 55:882–887

    PubMed  CAS  Google Scholar 

  63. Kalsner S (1978) Prostaglandin mediated relaxation of coronary artery strips under hypoxia. Prostaglandins Med 1:231–239

    Article  PubMed  CAS  Google Scholar 

  64. Kamekura I, Okumura K, Matsui H, Murase K, Mokuno S, Toki Y, Nakashima Y, Ito T (1999) Mechanisms of hypoxic coronary vasodilatation in isolated perfused rat hearts. J Cardiovasc Pharmacol 33:836–842

    Article  PubMed  CAS  Google Scholar 

  65. Kerkhof CJ, Van Der Linden PJ, Sipkema P (2002) Role of myocardium and endothelium in coronary vascular smooth muscle responses to hypoxia. Am J Physiol Heart Circ Physiol 282:H1296–H1303

    PubMed  CAS  Google Scholar 

  66. King RB, Bassingthwaighte JB, Hales JR, Rowell LB (1985) Stability of heterogeneity of myocardial blood flow in normal awake baboons. Circ Res 57:285–295

    PubMed  CAS  Google Scholar 

  67. Kingsbury MP, Robinson H, Flores NA, Sheridan DJ (2001) Investigation of mechanisms that mediate reactive hyperaemia in guinea-pig hearts: role of K(ATP) channels, adenosine, nitric oxide and prostaglandins. Br J Pharmacol 132:1209–1216

    Article  PubMed  CAS  Google Scholar 

  68. Komalavilas P, Mehta S, Wingard CJ, Dransfield DT, Bhalla J, Woodrum JE, Molinaro JR, Brophy CM (2001) PI3-kinase/ Akt modulates vascular smooth muscle tone via cAMP signaling pathways. J Appl Physiol 91:1819–1827

    PubMed  CAS  Google Scholar 

  69. Koyano T, Kakei M, Nakashima H, Yoshinaga M, Matsuoka T, Tanaka H (1993) ATP-regulated K+ channels are modulated by intracellular H+ in guinea-pig ventricular cells. J Physiol 463:747–766

    PubMed  CAS  Google Scholar 

  70. Kroll K, Kinzie DJ, Gustafson LA (1997) Open-system kinetics of myocardial phosphoenergetics during coronary underperfusion. Am J Physiol 272:H2563–H2576

    PubMed  CAS  Google Scholar 

  71. Liu Q (1999) Constriction to hypoxiareoxygenation in isolated mouse coronary arteries: role of endothelium and superoxide. J Appl Physiol 87:1392–1396

    PubMed  CAS  Google Scholar 

  72. Liu Y, Gutterman DD (2004) Cellular origin of EDHF (H2O2) released from human coronary arterioles in response to shear stress. Am Heart Assoc Scientific Sessions, Abstract 14327

  73. Meeks MK, Ripley ML, Jin Z, Rembold CM (2005) Heat shock protein 20-mediated force suppression in forskolin-relaxed swine carotid artery. Am J Physiol Cell Physiol 288:C633–C639

    Article  PubMed  CAS  Google Scholar 

  74. Merkus D, Haitsma DB, Fung TY, Assen YJ, Verdouw PD, Duncker DJ (2003) Coronary blood flow regulation in exercising swine involves parallel rather than redundant vasodilator pathways. Am J Physiol Heart Circ Physiol 285:H424–H433

    PubMed  CAS  Google Scholar 

  75. Merkus D, Hoeweling B, Zarbanoui A, Duncker DJ (2004) Interaction between prostanoids and nitric oxide in regulation of systemic, pulmonary, and coronary vascular tone in exercising swine. Am J Physiol 286:H1114–H1123

    CAS  Google Scholar 

  76. Michiels C, Arnould T, Knott I, Dieu M, Remacle J (1993) Stimulation of prostaglandin synthesis by human endothelial cells exposed to hypoxia. Am J Physiol 264:C866–C874

    PubMed  CAS  Google Scholar 

  77. Michiels C, Renard P, Bouaziz N, Heck N, Eliaers F, Ninane N, Quarck R, Holvoet P, Raes M (2002) Identification of the phospholipase A(2) isoforms that contribute to arachidonic acid release in hypoxic endothelial cells: limits of phospholipase A(2) inhibitors. Biochem Pharmacol 63:321–332

    Article  PubMed  CAS  Google Scholar 

  78. Miura H, Liu Y, Gutterman DD (1999) Human coronary arteriolar dilation to bradykinin depends on membrane hyperpolarization: contribution of nitric oxide and Ca2+-activated K+ channels. Circulation 99:3132–3138

    PubMed  CAS  Google Scholar 

  79. Mortensen UM, Nielsen-Kudsk JE, Jakobsen P, Nielsen TT (2003) Glibenclamide blunts coronary flow reserve induced by adenosine and dipyridamole. Scand Cardiovasc J 37:247–252

    Article  PubMed  CAS  Google Scholar 

  80. Nakhostine N, Lamontagne D (1994) Contribution of prostaglandins in hypoxia-induced vasodilation in isolated rabbit hearts. Relation to adenosine and KATP channels. Pflugers Arch 428:526–532

    Article  PubMed  CAS  Google Scholar 

  81. Nakhostine N, Laurent CE, Nadeau R, Cardinal R, Lamontagne D (1995) Hypoxia-induced release of prostaglandins: mechanisms and sources of production in coronary resistance vessels of the isolated rabbit heart. Can J Physiol Pharmacol 73:1742–1749

    PubMed  CAS  Google Scholar 

  82. Needleman P, Key SL, Isakson PC, Kulkarni PS (1975) Relationship between oxygen tension,coronary vasodilation and prostaglandin biosynthesis in the isolated rabbit heart. Prostaglandins 9:123–134

    Article  PubMed  CAS  Google Scholar 

  83. Newby AC, Worku Y, Holmquist CA (1985) Adenosine formation. Evidence for a direct biochemical link with energy metabolism. Adv Myocardiol 6:273–284

    PubMed  CAS  Google Scholar 

  84. Niiya K, Uchida S, Tsuji T, Olsson RA (1994) Glibenclamide reduces the coronary vasoactivity of adenosine receptor agonists. J Pharmacol Exp Ther 271:14–19

    PubMed  CAS  Google Scholar 

  85. Phillis JW, O’Regan MH, Song D (1999) Further evidence for the role of adenosine in hypercapnia/acidosis-evoked coronary flow regulation. Gen Pharmacol 33:431–437

    Article  PubMed  CAS  Google Scholar 

  86. Phillis JW, Song D, O’Regan MH (1998) The role of adenosine in rat coronary flow regulation during respiratory and metabolic acidosis. Eur J Pharmacol 356:199–206

    Article  PubMed  CAS  Google Scholar 

  87. Phillis JW, Song D, O’Regan MH (2000) Mechanisms involved in coronary artery dilatation during respiratory acidosis in the isolated perfused rat heart. Basic Res Cardiol 95:93–97

    Article  PubMed  CAS  Google Scholar 

  88. Pittman RN (1986) Interaction between oxygen and the blood vessel wall. Can J Cardiol 2:124–131

    PubMed  CAS  Google Scholar 

  89. Poburko D, Lee CH, van Bremen C (2004) Vascular smooth muscle mitochondria at the cross roads of Ca(2+) regulation. Cell Calcium 35:509–521

    Article  PubMed  CAS  Google Scholar 

  90. Randall MD (1995) The involvement of ATP-sensitive potassium channels and adenosine in the regulation of coronary flow in the isolated perfused rat heart. Br J Pharmacol 116:3068–3074

    PubMed  CAS  Google Scholar 

  91. Rembold CM, O’Connor M, Clarkson M, Wardle RL, Murphy RA (2001) Selected contribution: HSP20 phosphorylation in nitroglycerin- and forskolin-induced sustained reductions in swine carotid media tone. J Appl Physiol 91:1460–1466

    PubMed  CAS  Google Scholar 

  92. Richmond KN, Tune JD, Gorman MW, Feigl EO (1999) Role of K+ ATP channels in local metabolic coronary vasodilation. Am J Physiol 277:H2115–H2123

    PubMed  CAS  Google Scholar 

  93. Rosenmeier JB, Hansen J, Gonzalez-Alonso J (2004) Circulating ATP-induced vasodilatation overrides sympathetic vasoconstrictor activity in human skeletal muscle. J Physiol 558: 351–365

    Article  CAS  Google Scholar 

  94. Rossen JD, Oskarsson H, Minor Jr. RL, Talman CL, Winniford MD (1994) Effect of adenosine antagonism on metabolically mediated coronary vasodilation in humans. J Am Coll Cardiol 23:1421–1426

    Article  PubMed  CAS  Google Scholar 

  95. Ruiter JH, Spaan JAE, Laird JD (1978) Transient oxygen uptake during myocardial reactive hyperemia in the dog. Am J Physiol 235:H87–H94

    PubMed  CAS  Google Scholar 

  96. Saito S, Brzezinska AK, Chilian WM (2004) Mechanisms of coronary metabolic dilation: role of reactive oxygen species. Am Heart Assoc Scientific Sessions, Abstract 16838

    Google Scholar 

  97. Schrader J, Bardenheuer H (1981) Assessment of vasoactive metabolites released from the isolated guinea pig during heart hypoxia and beta-adrenergic stimulation. Basic Res Cardiol 76:365–368

    Article  PubMed  CAS  Google Scholar 

  98. Siegel G (1994) Membrane-physiologic reaction of arteriosclerotic coronary vessels to hypoxia in man. Vasa 23:205–213

    PubMed  CAS  Google Scholar 

  99. Smolenski RT, Schrader J, de Groot H, Deussen A (1991) Oxygen partial pressure and free intracellular adenosine of isolated cardiomyocytes. Am J Physiol 260:C708–C714

    PubMed  CAS  Google Scholar 

  100. Song D, O’Regan MH, Phillis JW (1999) Role of nitric oxide in rat coronary flow regulation during respiratory and metabolic acidosis. Gen Pharmacol 32:571–575

    Article  PubMed  CAS  Google Scholar 

  101. Stowe DF (1981) Heart bioassay of effluent of isolated, perfused guinea pig hearts to examine the role of metabolites regulating coronary flow during hypoxia. Basic Res Cardiol 76:359–364

    Article  PubMed  CAS  Google Scholar 

  102. Talukder MA, Morrison RR, Jacobson MA, Jacobson KA, Ledent C, Mustafa SJ (2002) Targeted deletion of adenosine A(3) receptors augments adenosine- induced coronary flow in isolated mouse heart. Am J Physiol Heart Circ Physiol 282:H2183–H2189

    PubMed  CAS  Google Scholar 

  103. Talukder MA, Morrison RR, Ledent C, Mustafa SJ (2003) Endogenous adenosine increases coronary flow by activation of both A2A and A2B receptors in mice. J Cardiovasc Pharmacol 41:562–570

    Article  PubMed  CAS  Google Scholar 

  104. Talukder MA, Morrison RR, Mustafa SJ (2002) Comparison of the vascular effects of adenosine in isolated mouse heart and aorta. Am J Physiol Heart Circ Physiol 282:H49–H57

    PubMed  CAS  Google Scholar 

  105. Traverse JH, Nesmelov YE, Crampton M, Lindstrom P, Thomas DD, Bache RJ (2004) Measurement of myocardial free radical production during exercise using EPR spectroscopy. Am Heart Assoc Scientific Sessions, Abstract 7911

  106. Tune JD, Richmond KN, Gorman MW, Feigl EO (2002) K(ATP)(+) channels, nitric oxide, and adenosine are not required for local metabolic coronary vasodilation. Am J Physiol Heart Circ Physiol 280:H868–H875

    Google Scholar 

  107. Tune JD, Richmond KN, Gorman MW, Feigl EO (2002) Control of coronary blood flow during exercise. Exp Biol Med 227:238–250

    CAS  Google Scholar 

  108. Tune JD, Richmond KN, Gorman MW, Olsson RA, Feigl EO (2001) Adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise. Am J Physiol Heart Circ Physiol 278:H74–H84

    Google Scholar 

  109. Vedernikov YP, Graser T, Leisner H, Tiedt N (1991) Effect of hypoxia on endothelium-dependent relaxation of porcine coronary arteries and veins. Biomed Biochim Acta 50:257–263

    PubMed  CAS  Google Scholar 

  110. Vedernikov YP, Graser T, Li DS (1990) Hypoxic and posthypoxic responses in isolated coronary arteries and veins: role of endothelium. Biomed Biochim Acta 49:1177–1184

    PubMed  CAS  Google Scholar 

  111. von Beckerath N, Cyrys S, Dischner A, Daut J (1991) Hypoxic vasodilatation in isolated, perfused guinea-pig heart: an analysis of the underlying mechanisms. 442:297–319

  112. Vretzakis G, Ferdi E, Papaziogas B, Dragoumanis C, Pneumatikos J, Tsangaris I, Tsakiridis K, Konstantinou F (2004) Coronary sinus venoarterial CO2 difference in different hemodynamic states. Acta Anaesthesiol Belg 55:221–227

    PubMed  CAS  Google Scholar 

  113. Wang X, Wu J, Li L, Chen F, Wang R, Jiang C (2003) Hypercapnic acidosis activates KATP channels in vascular smooth muscles. Circ Res 92:1225–1232

    Article  PubMed  CAS  Google Scholar 

  114. Wei HM, Kang YH, Merrill GF (1988) Coronary vasodilation during global myocardial hypoxia: effects of adenosine deaminase. Am J Physiol 254:H1004–H1009

    PubMed  CAS  Google Scholar 

  115. Wexels JC, (1985) Effects of carbon dioxide and pH on myocardial bloodflow and metabolism in the dog. Clin Physiol 5(6):575–588

    PubMed  CAS  Google Scholar 

  116. Wolfenden R, Sharpless TK, Allan R (1967) Substrate binding by adenosine deaminase. Specificity, pH dependence, and competition by mercurials. J Biol Chem 242:977–983

    PubMed  CAS  Google Scholar 

  117. Wolin MS (2000) Interactions of oxidants with vascular signaling systems. Arterioscler Thromb Vasc Biol 20:1430–1442

    PubMed  CAS  Google Scholar 

  118. Xhonneux R, Schaper W (1969) The pO2 in the coronary sinus: correlation studies with other circulatory and respiratory parameters based on a population of 500 dogs. Prog Respir Res 3:89–93

    Google Scholar 

  119. Xu Z, Park SS, Mueller RA, Bagnell RC, Patterson C, Boysen PG (2005) Adenosine produces nitric oxide and prevents mitochondrial oxidant damage in rat cardiomyocytes. Cardiovasc Res 65:803–812

    Article  PubMed  CAS  Google Scholar 

  120. Yada T, Richmond KN, Van Bibber R, Kroll K, Feigl EO (1999) Role of adenosine in local metabolic coronary vasodilation. Am J Physiol 276:H1425–H1433

    PubMed  CAS  Google Scholar 

  121. Yamamoto M, Egashira K, Arimura K, Tada H, Shimokawa H, Takeshita A (2000) Coronary vascular K+ ATP channels contribute to the maintenance of myocardial perfusion in dogs with pacing-induced heart failure. Jpn Circ J 64:701–707

    Article  PubMed  CAS  Google Scholar 

  122. Zhang C, Brzezinska AK, Chilian WM (2004) Hydrogen peroxide is a coronary vasodilator linking myocardial metabolism to coronary blood flow. Am Heart Assoc Scientific Sessions, Abstract 9879

  123. Zhang C, Hein TW, Kuo L (2000) Transmural difference in coronary arteriolar dilation to adenosine: effect of luminal pressure and K(ATP) channels. Am J Physiol Heart Circ Physiol 279:H2612–H2619

    PubMed  CAS  Google Scholar 

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Correspondence to A. Deussen.

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Deussen, A., Brand, M., Pexa, A. et al. Metabolic coronary flow regulation—Current concepts. Basic Res Cardiol 101, 453–464 (2006). https://doi.org/10.1007/s00395-006-0621-4

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  • DOI: https://doi.org/10.1007/s00395-006-0621-4

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