Targeting adenosine receptors in the development of cardiovascular therapeutics

Expert Review of Clinical Pharmacology

Volumn 5, Issue 2, 2012, Pages 199-218

  Riksen, Niels P ^a   Rongen, Gerard A ^a  

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

adenosine; atherosclerosis; cardiac arrhythmias; cardiac remodeling; ischemiareperfusion injury

Indexed keywords

3 DEAZAADENOSINE; 4 [7 [[1 [(3 CHLORO 2 THIENYL)METHYL]PROPYL]AMINO] 3H IMIDAZO[4,5 B]PYRIDIN 3 YL] N ETHYL 2,3 DIHYDROXYCYCLOPENTANECARBOXAMIDE; 5 AMINO 4 IMIDAZOLECARBOXAMIDE RIBOSIDE; ADENOSINE; ADENOSINE A1 RECEPTOR; ADENOSINE A1 RECEPTOR AGONIST; ADENOSINE A2A RECEPTOR; ADENOSINE A2B RECEPTOR; ADENOSINE A3 RECEPTOR; ADENOSINE KINASE; ADENOSINE MONOPHOSPHATE DEAMINASE; APYRASE; ATROPINE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CARVEDILOL; CVT 3619; DIPYRIDAMOLE; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INTERLEUKIN 10; METFORMIN; METHOTREXATE; NEBIVOLOL; NORADRENALIN; ROLOFYLLINE; ROSUVASTATIN; TECADENOSON; UNCLASSIFIED DRUG; VASCULAR CELL ADHESION MOLECULE 1;

ACUTE HEART INFARCTION; ADRENERGIC TRANSMISSION; ATHEROGENESIS; ATHEROSCLEROSIS; ATRIOVENTRICULAR CONDUCTION; BINDING AFFINITY; BLOOD CLOT LYSIS; BLOOD VESSEL TONE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR EFFECT; CELL PROLIFERATION; CORONARY ARTERY BLOOD FLOW; CORONARY ARTERY BYPASS GRAFT; CYTOKINE PRODUCTION; DIABETES MELLITUS; DRUG EFFICACY; DRUG HALF LIFE; DRUG TARGETING; ENDOTHELIUM CELL; EXERCISE TEST; HEART ATRIUM FIBRILLATION; HEART CONTRACTION; HEART FAILURE; HEART INFARCTION; HEART INFARCTION SIZE; HEART MUSCLE CELL; HEART MUSCLE ISCHEMIA; HEART PROTECTION; HEART SUPRAVENTRICULAR ARRHYTHMIA; HEART VENTRICLE HYPERTROPHY; HEART VENTRICLE REMODELING; HUMAN; IMMUNOHISTOCHEMISTRY; INSULIN RESISTANCE; INSULIN SENSITIVITY; ISCHEMIC PRECONDITIONING; MITOCHONDRIAL RESPIRATION; NEOINTIMA; NON ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; NONHUMAN; NORADRENALIN RELEASE; PERCUTANEOUS CORONARY INTERVENTION; POLYMORPHONUCLEAR CELL; RENIN RELEASE; REPERFUSION INJURY; REVIEW; SCINTIGRAPHY; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; SODIUM ABSORPTION; ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; SUPRAVENTRICULAR TACHYCARDIA; THROMBOCYTE AGGREGATION; TREATMENT OUTCOME; UMBILICAL VEIN ENDOTHELIAL CELL; VASCULAR ENDOTHELIUM; VASOCONSTRICTION; VASODILATATION;

ADENOSINE; ANIMALS; ARRHYTHMIAS, CARDIAC; ATHEROSCLEROSIS; CARDIOVASCULAR AGENTS; CARDIOVASCULAR DISEASES; HUMANS; INSULIN; KIDNEY; RECEPTORS, PURINERGIC P1; REPERFUSION INJURY; SIGNAL TRANSDUCTION;

EID: 84858411451     PISSN: 17512433     EISSN: 17512441     Source Type: Journal    
DOI: 10.1586/ecp.12.8     Document Type: Review

References (250)

1. Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N. Engl. J. Med. 357(11), 1121-1135 (2007).
2. Drury AN, Szent-Gyorgyi A. The physiological activity of adenine compounds with special reference to their action upon the mammalian heart. J. Physiol. 68, 213-237 (1929).
3. Fredholm BB. Adenosine, an endogenous distress signal, modulates tissue damage and repair. Cell Death. Differ. 14(7), 1315-1323 (2007).
4. Linden J. Adenosine in tissue protection and tissue regeneration. Mol. Pharmacol. 67(5), 1385-1387 (2005).
5. Deussen A. Metabolic flux rates of adenosine in the heart. Naunyn Schmiedebergs Arch. Pharmacol. 362(4-5), 351-363 (2000).
6. Ueland PM. Pharmacological and biochemical aspects of S-adenosylhomocysteine and S-adenosylhomocysteine hydrolase. Pharmacol. Rev. 34(3), 223-253 (1982).
7. Lloyd HG, Deussen A, Wuppermann H, Schrader J. The transmethylation pathway as a source for adenosine in the isolated guinea-pig heart. Biochem. J. 252(2), 489-494 (1988).
8. Burnstock G, Sneddon P. Evidence for ATP and noradrenaline as cotransmitters in sympathetic nerves. Clin Sci. (Lond.) 68(Suppl. 10), S89-S92 (1985).
9. Born GV, Kratzer MA. Source and concentration of extracellular adenosine triphosphate during haemostasis in rats, rabbits and man. J. Physiol. 354, 419-429 (1984).
10. Bergfeld GR, Forrester T. Release of ATP from human erythrocytes in response to a brief period of hypoxia and hypercapnia. Cardiovasc. Res. 26(1), 40-47 (1992).
11. Borst MM, Schrader J. Adenine nucleotide release from isolated perfused guinea pig hearts and extracellular formation of adenosine. Circ. Res. 68(3), 797-806 (1991).
12. Clarke TC, Williams OJ, Martin PE, Evans WH. ATP release by cardiac myocytes in a simulated ischaemia model: Inhibition by a connexin mimetic and enhancement by an antiarrhythmic peptide. Eur. J. Pharmacol. 605(1-3), 9-14 (2009).
13. Elliott MR, Chekeni FB, Trampont PC et al. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461(7261), 282-286 (2009).
14. Zoref-Shani E, Kessler-Icekson G, Sperling O. Pathways of adenine nucleotide catabolism in primary rat cardiomyocyte cultures. J. Mol. Cell Cardiol. 20(1), 23-33 (1988).
15. Chen W, Gueron M. AMP degradation in the perfused rat heart during 2-deoxy-d-glucose perfusion and anoxia. Part II: The determination of the degradation pathways using an adenosine deaminase inhibitor. J. Mol. Cell Cardiol. 28(10), 2175-2182 (1996).
16. Deussen A, Stappert M, Schafer S, Kelm M. Quantification of extracellular and intracellular adenosine production: understanding the transmembranous concentration gradient. Circulation 99(15), 2041-2047 (1999).
17. Lasley RD, Hegge JO, Noble MA, Mentzer RM. Evidence that cytosolic and ecto 5′-nucleotidases contribute equally to increased interstitial adenosine concentration during porcine myocardial ischemia. Basic Res. Cardiol. 94(3), 199-207 (1999).
18. Van Wylen DG, Schmit TJ, Lasley RD, Gingell RL, Mentzer RM Jr. Cardiac microdialysis in isolated rat hearts: Interstitial purine metabolites during ischemia. Am. J. Physiol. 262(6 Pt 2), H1934-H1938 (1992).
19. Van Belle H, Goossens F, Wynants J. Formation and release of purine catabolites during hypoperfusion, anoxia, and ischemia. Am. J. Physiol. 252(5 Pt 2), H886-H893 (1987).
20. Darvish A, Pomerantz RW, Zografides PG, Metting PJ. Contribution of cytosolic and membrane-bound 5′-nucleotidases to cardiac adenosine production. Am. J. Physiol. 271(5 Pt 2), H2162-H2167 (1996).
21. Sato T, Obata T, Yamanaka Y, Arita M. Stimulation of alpha 1-adrenoceptors and protein kinase C-mediated activation of ecto-5′- nucleotidase in rat hearts in vivo. J. Physiol. 503(Pt 1), 119-127 (1997).
22. Synnestvedt K, Furuta GT, Comerford KM et al. Ecto-5′-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. J. Clin. Invest 110(7), 993-1002 (2002).
23. Kobayashi S, Zimmermann H, Millhorn DE. Chronic hypoxia enhances adenosine release in rat PC12 cells by altering adenosine metabolism and membrane transport. J. Neurochem. 74(2), 621-632 (2000).
24. Schutz W, Schrader J, Gerlach E. Different sites of adenosine formation in the heart. Am. J. Physiol. 240(6), H963-H970 (1981).
25. Moser GH, Schrader J, Deussen A. Turnover of adenosine in plasma of human and dog blood. Am. J. Physiol. 256(4 Pt 1), C799-C806 (1989).
26. Van Wylen DG, Willis J, Sodhi J et al. Cardiac microdialysis to estimate interstitial adenosine and coronary blood flow. Am. J. Physiol. 258(6 Pt 2), H1642-H1649 (1990).
27. Fredholm BB, Ijzerman AP, Jacobson KA, Klotz KN, Linden J. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol. Rev. 53(4), 527-552 (2001).
28. Fredholm BB, Ijzerman AP, Jacobson KA, Linden J, Muller CE. International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors - An update. Pharmacol. Rev. 63(1), 1-34 (2011).
29. Schulte G, Fredholm BB. Signalling from adenosine receptors to mitogen-activated protein kinases. Cell. Signal. 15(9), 813-827 (2003).
30. Yan L, Burbiel JC, Maass A, Muller CE. Adenosine receptor agonists: From basic medicinal chemistry to clinical development. Expert Opin. Emerg. Drugs 8(2), 537-576 (2003).
31. Fredholm BB, Irenius E, Kull B, Schulte G. Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells. Biochem. Pharmacol. 61(4), 443-448 (2001).
32. Arslan G, Kull B, Fredholm BB. Signaling via A2A adenosine receptor in four PC12 cell clones. Naunyn Schmiedebergs Arch. Pharmacol. 359(1), 28-32 (1999).
33. Khoa ND, Montesinos MC, Reiss AB et al. Inflammatory cytokines regulate function and expression of adenosine A(2A) receptors in human monocytic THP-1 cells. J. Immunol. 167(7), 4026-4032 (2001).
34. Murphree LJ, Sullivan GW, Marshall MA, Linden J. Lipopolysaccharide rapidly modifies adenosine receptor transcripts in murine and human macrophages: Role of NF-kappaB in A(2A) adenosine receptor induction. Biochem. J. 391(Pt 3), 575-580 (2005).
35. Nemeth ZH, Leibovich SJ, Deitch EA et al. cDNA microarray analysis reveals a nuclear factor-kappaB-independent regulation of macrophage function by adenosine. J. Pharmacol. Exp. Ther. 306(3), 1042-1049 (2003).
36. Feoktistov I, Ryzhov S, Zhong H et al. Hypoxia modulates adenosine receptors in human endothelial and smooth muscle cells toward an A2B angiogenic phenotype. Hypertension 44(5), 649-654 (2004).
37. Kong T, Westerman KA, Faigle M, Eltzschig HK, Colgan SP. HIF-dependent induction of adenosine A2B receptor in hypoxia. FASEB J. 20(13), 2242-2250 (2006).
38. Ahmad A, Ahmad S, Glover L et al. Adenosine A2A receptor is a unique angiogenic target of HIF-2alpha in pulmonary endothelial cells. Proc. Natl Acad. Sci. USA 106(26), 10684-10689 (2009).
39. Brown ST, Reyes EP, Nurse CA. Chronic hypoxia upregulates adenosine 2a receptor expression in chromaffin cells via hypoxia inducible factor-2alpha: Role in modulating secretion. Biochem. Biophys. Res. Commun. 412(3), 466-472 (2011).
40. Riksen NP, Rongen GA, Yellon D, Smits P. Human in vivo research on the vascular effects of adenosine. Eur. J. Pharmacol. 585(2-3), 220-227 (2008).
41. Rongen GA, Floras JS, Lenders JWM, Thien T, Smits P. Cardiovascular pharmacology of purines. Clin. Sci. 92, 13-24 (1997).
42. Balcells E, Suarez J, Rubio R. Functional role of intravascular coronary endothelial adenosine receptors. Eur. J. Pharmacol. 210(1), 1-9 (1992).
43. Riksen NP, van Ginneken EE, van den Broek PH, Smits P, Rongen GA. In vivo evidence against a role for adenosine in the exercise pressor reflex in humans. J. Appl. Physiol. 99(2), 522-527 (2005).
44. Smits P, Williams SB, Lipson DE et al. Endothelial release of nitric oxide contributes to the vasodilator effect of adenosine in humans. Circulation 92(8), 2135-2141 (1995).
45. Costa F, Biaggioni I. Role of nitric oxide in adenosine-induced vasodilation in humans. Hypertension 31(5), 1061-1064 (1998).
46. Nayeem MA, Zeldin DC, Boegehold MA, Falck JR. Salt modulates vascular response through adenosine A(2A) receptor in eNOS-null mice: Role of CYP450 epoxygenase and soluble epoxide hydrolase. Mol. Cell Biochem. 350(1-2), 101-111 (2011).
47. Nayeem MA, Poloyac SM, Falck JR et al. Role of CYP epoxygenases in A2A AR-mediated relaxation using A2A AR-null and wild-type mice. Am. J. Physiol. Heart Circ. Physiol. 295(5), H2068-H2078 (2008).
48. Sanjani MS, Teng B, Krahn T et al. Contributions of A2A and A2B adenosine receptors in coronary flow responses in relation to the KATP channel using A2B and A2A/2B double-knockout mice. Am. J. Physiol. Heart Circ. Physiol. 301(6), H2322-H2333 (2011).
49. Ponnoth DS, Sanjani MS, Ledent C et al. Absence of adenosine-mediated aortic relaxation in A(2A) adenosine receptor knockout mice. Am. J. Physiol. Heart Circ. Physiol. 297(5), H1655-H1660 (2009).
50. Flood A, Headrick JP. Functional characterization of coronary vascular adenosine receptors in the mouse. Br. J. Pharmacol. 133(7), 1063-1072 (2001).
51. Bijlstra P, van Ginneken EE, Huls M et al. Glyburide inhibits dipyridamole-induced forearm vasodilation but not adenosine-induced forearm vasodilation. Clin. Pharmacol. Ther. 75(3), 147-156 (2004).
52. Osswald H, Hermes HH, Nabakowski G. Role of adenosine in signal transmission of tubuloglomerular feedback. Kidney Int. Suppl. 12, S136-S142 (1982).
53. Castrop H, Huang Y, Hashimoto S et al. Impairment of tubuloglomerular feedback regulation of GFR in ecto-5′-nucleotidase/CD73-deficient mice. J. Clin. Invest. 114(5), 634-642 (2004).
54. Ren Y, Garvin JL, Liu R, Carretero OA. Role of macula densa adenosine triphosphate (ATP) in tubuloglomerular feedback. Kidney Int. 66(4), 1479-1485 (2004).
55. Carlstrom M, Wilcox CS, Welch WJ. Adenosine A(2) receptors modulate tubuloglomerular feedback. Am. J. Physiol. Renal Physiol. 299(2), F412-F417 (2010).
56. Carlstrom M, Wilcox CS, Welch WJ. Adenosine A2A receptor activation attenuates tubuloglomerular feedback responses by stimulation of endothelial nitric oxide synthase. Am. J. Physiol. Renal Physiol. 300(2), F457-F464 (2011).
57. Wierema TK, Houben AJ, Kroon AA et al. Mechanisms of adenosine-induced renal vasodilatation in hypertensive patients. J. Hypertens. 23(9), 1731-1736 (2005).
58. Liclican EL, McGiff JC, Pedraza PL et al. Exaggerated response to adenosine in kidneys from high salt-fed rats: Role of epoxyeicosatrienoic acids. Am. J. Physiol. Renal Physiol. 289(2), F386-F392 (2005).
59. Al-Mashhadi RH, Skott O, Vanhoutte PM, Hansen PB. Activation of A(2) adenosine receptors dilates cortical efferent arterioles in mouse. Kidney Int. 75(8), 793-799 (2009).
60. Smits P, de Leeuw PW, van Es PN, Postma CT, Thien T. Adenosine induces renal vasodilation in primary hypertensive patients. J. Hypertens. Suppl. 9(6), S214-S215 (1991).
61. Wang D, Belardinelli L. Mechanism of the negative inotropic effect of adenosine in guinea pig atrial myocytes. Am. J. Physiol. 267(6 Pt 2), H2420-H2429 (1994).
62. Wesley RC Jr, Boykin MT, Belardinelli L. Role of adenosine as mediator of bradyarrhythmias during hypoxia in isolated guinea pig hearts. Cardiovasc. Res. 20(10), 752-759 (1986).
63. Strickberger SA, Man KC, Daoud EG et al. Adenosine-induced atrial arrhythmia: A prospective analysis. Ann. Intern. Med. 127, 417-422 (1997).
64. Kabell G, Buchanan LV, Gibson JK, Belardinelli L. Effects of adenosine on atrial refractoriness and arrhythmias. Cardiovasc. Res. 28(9), 1385-1389 (1994).
65. Rongen GA, Lenders JWM, Lambrou G et al. Presynaptic inhibition of norepinephrine release from sympathetic nerve endings by endogenous adenosine. Hypertension 27, 933-938 (1996).
66. Burnstock G. Physiology and pathophysiology of purinergic neurotransmission. Physiol. Rev. 87(2), 659-797 (2007).
67. Smits P, Lenders JW, Willemsen JJ, Thien T. Adenosine attenuates the response to sympathetic stimuli in humans. Hypertension 18(2), 216-223 (1991).
68. Rongen GA, Brooks SC, Ando S, Abramson BL, Floras JS. Angiotensin AT1 receptor blockade abolishes the reflex sympatho-excitatory response to adenosine. J. Clin. Invest. 101, 769-776 (1998).
69. Rongen GA, Senn BL, Ando S et al. Comparison of hemodynamic and sympathoneural responses to adenosine and lower body negative pressure in man. Can. J. Physiol. Pharmacol. 75, 128-134 (1997).
70. Rongen GA, Brooks SC, Pollard MJ et al. Effect of adenosine on heart rate variability in humans. Clin. Sci. 96(6), 597-604 (1999).
71. Timmers HJ, Rongen GA, Karemaker JM et al. The role of carotid chemoreceptors in the sympathetic activation by adenosine in humans. Clin. Sci. 106(1), 75-82 (2004).
72. Edlund A, Ohlsen H, Sollevi A. Renal effects of local infusion of adenosine in man. Clin. Sci. 87(2), 143-149 (1994).
73. Katholi RE, Whitlow PL, Hageman GR, Woods WT. Intrarenal adenosine produces hypertension by activating the sympathetic nervous system via the renal nerves in the dog. J. Hypertens. 2, 349-359 (1984).
74. Stella A. The kidney as a sensor: Functional evidence. J. Hypertens. Suppl. 10, S113-S119 (1992).
75. Wijeysundera HC, Parmar G, Rongen GA, Floras JS. Reflex systemic sympatho-neural response to brachial adenosine infusion in treated heart failure. Eur. J. Heart Fail. 13(5), 475-481 (2011).
76. Fisher JW and Nakashima J. The role of hypoxia in renal production of erythropoietin. Cancer 70, 928-939 (1992).
77. Ozuyaman B, Ding Z, Buchheiser A et al. Adenosine produced via the CD73/ecto-5′-nucleotidase pathway has no impact on erythropoietin production but is associated with reduced kidney weight. Pflugers Arch. 452(3), 324-331 (2006).
78. Arend LJ, Haramati A, Thompson CI, Spielman WS. Adenosine-induced decrease in renin release: Dissociation from hemodynamic effects. Am. J. Physiol. 247, F447-F452 (1984).
79. Spielman WS. Antagonistic effect of theophylline on the adenosine-induced decreased in renin release. Am. J. Physiol. 247, F246-F251 (1984).
80. Lorenz JN, Weihprecht H, He XR et al. Effects of adenosine and angiotensin on macula densa-stimulated renin secretion. Am. J Physiol. 265, F187-F194 (1993).
81. Biaggioni I. Contrasting excitatory and inhibitory effects of adenosine in blood pressure regulation. Hypertension 20(4), 457-465 (1992).
82. Miura K, Okumura M, Yamanaka S, Kim S, Iwao H. Effects of activation of renal adenosine A2 receptor on renal function and renin release in dogs. Jpn J. Pharmacol. 80(2), 173-176 (1999).
83. Taddei S, Virdis A, Favilla S, Salvetti A. Adenosine activates a vascular renin-angiotensin system in hypertensive subjects. Hypertension 19, 672-675 (1992).
84. DiSole F. Adenosine and renal tubular function. Curr. Opin. Nephrol. Hypertens. 17(4), 399-407 (2008).
85. Nagashima K and Karasawa A. Effects of KW-3902 (8-(noradamantan-3-yl)-1, 3-dipropylxanthine), an adenosine A1-receptor antagonist, on urinary excretions of various electrolytes in rats. Biol. Pharm. Bull. 19(7), 940-943 (1996).
86. Givertz MM, Massie BM, Fields TK, Pearson LL, Dittrich HC. The effects of KW-3902, an adenosine A1-receptor antagonist,on diuresis and renal function in patients with acute decompensated heart failure and renal impairment or diuretic resistance. J. Am. Coll. Cardiol. 50(16), 1551-1560 (2007).
87. Amisten S, Braun OO, Bengtsson A, Erlinge D. Gene expression profiling for the identification of G-protein coupled receptors in human platelets. Thromb. Res. 122(1), 47-57 (2008).
88. Cristalli G, Vittori S, Thompson RD et al. Inhibition of platelet aggregation by adenosine receptor agonists. Naunyn Schmiedebergs Arch. Pharmacol. 349, 644-650 (1994).
89. Sandoli D, Chiu PJ, Chintala M, Dionisotti S, Ongini E. In vivo and ex vivo effects of adenosine A1 and A2 receptor agonists on platelet aggregation in the rabbit. Eur. J. Pharmacol. 259(1), 43-49 (1994).
90. Kitakaze M, Hori M, Sato H et al. Endogenous adenosine inhibits platelet aggregation during myocardial ischemia in dogs. Circ. Res. 69(5), 1402-1408 (1991).
91. Varani K, Portaluppi F, Merighi S et al. Caffeine alters A2A adenosine receptors and their function in human platelets. Circulation 99(19), 2499-2502 (1999).
92. Milne GR and Palmer TM. Anti-inflammatory and immunosuppressive effects of the A2A adenosine receptor. ScientificWorldJournal 11, 320-339 (2011).
93. Hasko G, Linden J, Cronstein B, Pacher P. Adenosine receptors: Therapeutic aspects for inflammatory and immune diseases. Nat. Rev. Drug Discov. 7(9), 759-770 (2008).
94. Cronstein BN, Levin RI, Philips M et al. Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors. J. Immunol. 148, 2201-2206 (1992).
95. Aherne CM, Kewley EM, Eltzschig HK. The resurgence of A2B adenosine receptor signaling. Biochim. Biophys. Acta 1808(5), 1329-1339 (2011).
96. Linden J. New insights into the regulation of inflammation by adenosine. J. Clin. Invest. 116(7), 1835-1837 (2006).
97. Yang D, Zhang Y, Nguyen HG et al. The A2B adenosine receptor protects against inflammation and excessive vascular adhesion. J. Clin. Invest. 116(7), 1913-1923 (2006).
98. Yang D, Koupenova M, McCrann DJ et al. The A2b adenosine receptor protects against vascular injury. Proc. Natl Acad. Sci. USA 105(2), 792-796 (2008).
99. Koupenova M, Johnston-Cox H, Vezeridis A et al. The A2b adenosine receptor regulates hyperlipidemia and atherosclerosis. Circulation 125(2), 354-363 (2012).
100. Bouma MG, van den Wildenberg FA, Buurman WA. Adenosine inhibits cytokine release and expression of adhesion molecules by activated human endothelial cells. Am. J. Physiol. 270(2 Pt 1), C522-C529 (1996).
101. Blankenberg S, Barbaux S, Tiret L. Adhesion molecules and atherosclerosis. Atherosclerosis 170(2), 191-203 (2003).
102. Reiss AB, Rahman MM, Chan ES et al. Adenosine A2A receptor occupancy stimulates expression of proteins involved in reverse cholesterol transport and inhibits foam cell formation in macrophages. J. Leukoc. Biol. 76(3), 727-734 (2004).
103. Dubey RK, Gillespie DG, Mi Z, Jackson EK. Adenosine inhibits growth of human aortic smooth muscle cells via A2B receptors. Hypertension 31(1 Pt 2), 516-521 (1998).
104. Peyot ML, Gadeau AP, Dandre F et al. Extracellular adenosine induces apoptosis of human arterial smooth muscle cells via A(2b)-purinoceptor. Circ. Res. 86(1), 76-85 (2000).
105. Shen J, Halenda SP, Sturek M, Wilden PA. Novel mitogenic effect of adenosine on coronary artery smooth muscle cells: Role for the A1 adenosine receptor. Circ. Res. 96(9), 982-990 (2005).
106. Dubey RK, Gillespie DG, Jackson EK. Adenosine inhibits collagen and total protein synthesis in vascular smooth muscle cells. Hypertension 33(1 Pt 2), 190-194 (1999).
107. Dubey RK, Gillespie DG, Zacharia LC, Mi Z, Jackson EK. A(2b) receptors mediate the antimitogenic effects of adenosine in cardiac fibroblasts. Hypertension 37(2 Part 2), 716-721 (2001).
108. Cronstein BN. Adenosine receptors and fibrosis: A translational review. F1000 Biol. Rep. 3, 21 (2011).
109. Auchampach JA. Adenosine receptors and angiogenesis. Circ. Res. 101(11), 1075-1077 (2007).
110. Leibovich SJ, Chen JF, Pinhal-Enfield G et al. Synergistic up-regulation of vascular endothelial growth factor expression in murine macrophages by adenosine A(2A) receptor agonists and endotoxin. Am. J. Pathol. 160(6), 2231-2244 (2002).
111. McPherson JA, Barringhaus KG, Bishop GG et al. Adenosine A(2A) receptor stimulation reduces inflammation and neointimal growth in a murine carotid ligation model. Arterioscler. Thromb. Vasc. Biol. 21(5), 791-796 (2001).
112. Walker G, Langheinrich AC, Dennhauser E et al. 3-deazaadenosine prevents adhesion molecule expression and atherosclerotic lesion formation in the aortas of C57BL/6J mice. Arterioscler. Thromb. Vasc. Biol. 19(11), 2673-2679 (1999).
113. Koszalka P, Ozuyaman B, Huo Y et al. Targeted disruption of cd73/ecto-5′-nucleotidase alters thromboregulation and augments vascular inflammatory response. Circ. Res. 95(8), 814-821 (2004).
114. Zernecke A, Bidzhekov K, Ozuyaman B et al. CD73/ecto-5′- nucleotidase protects against vascular inflammation and neointima formation. Circulation 113(17), 2120-2127 (2006).
115. Buchheiser A, Ebner A, Burghoff S et al. Inactivation of CD73 promotes atherogenesis in apolipoprotein E-deficient mice. Cardiovasc. Res. 92(2), 338-347 (2011).
116. Wang H, Zhang W, Tang R et al. Adenosine receptor A2A deficiency in leukocytes increases arterial neointima formation in apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol. 30(5), 915-922 (2010).
117. Wang H, Zhang W, Zhu C et al. Inactivation of the adenosine A2A receptor protects apolipoprotein E-deficient mice from atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 29(7), 1046-1052 (2009).
118. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium. Circulation 74, 1124-1136 (1986).
119. Zhao ZQ, Corvera JS, Halkos ME et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: Comparison with ischemic preconditioning. Am. J. Physiol. Heart Circ. Physiol. 285(2), H579-H588 (2003).
120. Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 87, 893-899 (1993).
121. Thornton JD, Liu GS, Olsson RA, Downey JM. Intravenous pretreatment with A1-selective adenosine analogues protects the heart against infarction. Circulation 85(2), 659-665 (1992).
122. Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: united at reperfusion. Pharmacol. Ther. 116(2), 173-191 (2007).
123. Headrick JP, Peart JN, Reichelt ME, Haseler LJ. Adenosine and its receptors in the heart: Regulation, retaliation and adaptation. Biochim. Biophys. Acta 1808(5), 1413-1428 (2011).
124. Peart JN, Headrick JP. Adenosinergic cardioprotection: multiple receptors, multiple pathways. Pharmacol. Ther. 114(2), 208-221 (2007).
125. Jordan JE, Zhao ZQ, Sato H, Taft S, Vinten-Johansen J. Adenosine A2 receptor activation attenuates reperfusion injury by inhibiting neutrophil accumulation, superoxide generation and coronary endothelial adherence. J. Pharmacol. Exp. Ther. 280(1), 301-309 (1997).
126. Lasley RD, Jahania MS, Mentzer RM Jr. Beneficial effects of adenosine A(2a) agonist CGS-21680 in infarcted and stunned porcine myocardium. Am. J. Physiol. Heart Circ. Physiol. 280(4), H1660-H1666 (2001).
127. Yang Z, Linden J, Berr SS et al. Timing of adenosine 2A receptor stimulation relative to reperfusion has differential effects on infarct size and cardiac function as assessed in mice by MRI. Am. J. Physiol. Heart Circ. Physiol. 295(6), H2328-H2335 (2008).
128. Yang Z, Day YJ, Toufektsian MC et al. Infarct-sparing effect of A2A-adenosine receptor activation is due primarily to its action on lymphocytes. Circulation 111(17), 2190-2197 (2005).
129. 4+ T lymphocytes. Circulation 114(19), 2056-2064 (2006).
130. Kuno A, Critz SD, Cui L et al. Protein kinase C protects preconditioned rabbit hearts by increasing sensitivity of adenosine A2b-dependent signaling during early reperfusion. J. Mol. Cell Cardiol. 43(3), 262-271 (2007).
131. Philipp S, Yang XM, Cui L et al. Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade. Cardiovasc. Res. 70(2), 308-314 (2006).
132. Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc. Res. 79(3), 377-386 (2008).
133. Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling - concepts and clinical implications: A consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J. Am. Coll. Cardiol. 35(3), 569-582 (2000).
134. Dubey RK, Gillespie DG, Jackson EK. Adenosine inhibits collagen and protein synthesis in cardiac fibroblasts: Role of A2B receptors. Hypertension 31(4), 943-948 (1998).
135. Liao Y, Takashima S, Asano Y et al. Activation of adenosine A1 receptor attenuates cardiac hypertrophy and prevents heart failure in murine left ventricular pressure-overload model. Circ. Res. 93(8), 759-766 (2003).
136. Chung ES, Perlini S, Aurigemma GP et al. Effects of chronic adenosine uptake blockade on adrenergic responsiveness and left ventricular chamber function in pressure overload hypertrophy in the rat. J. Hypertens. 16(12 Pt 1), 1813-1822 (1998).
137. Wakeno M, Minamino T, Seguchi O et al. Long-term stimulation of adenosine A2b receptors begun after myocardial infarction prevents cardiac remodeling in rats. Circulation 114(18), 1923-1932 (2006).
138. Xu X, Fassett J, Hu X et al. Ecto-5′-nucleotidase deficiency exacerbates pressure-overload-induced left ventricular hypertrophy and dysfunction. Hypertension 51(6), 1557-1564 (2008).
139. Lu Z, Fassett J, Xu X et al. Adenosine A3 receptor deficiency exerts unanticipated protective effects on the pressure-overloaded left ventricle. Circulation 118(17), 1713-1721 (2008).
140. Challis RA, Budohoski L, McManus B, Newsholme EA. Effects of an adenosine-receptor antagonist on insulin-resistance in soleus muscle from obese Zucker rats. Biochem. J. 221(3), 915-917 (1984).
141. Vergauwen L, Hespel P, Richter EA. Adenosine receptors mediate synergistic stimulation of glucose uptake and transport by insulin and by contractions in rat skeletal muscle. J. Clin. Invest. 93, 974-981 (1994).
142. Dong Q, Ginsberg HN, Erlanger BF. Overexpression of the A1 adenosine receptor in adipose tissue protects mice from obesity-related insulin resistance. Diabetes Obes. Metab 3(5), 360-366 (2001).
143. Johansson SM, Lindgren E, Yang JN, Herling AW, Fredholm BB. Adenosine A1 receptors regulate lipolysis and lipogenesis in mouse adipose tissue-interactions with insulin. Eur. J. Pharmacol. 597(1-3), 92-101 (2008).
144. Faulhaber-Walter R, Jou W, Mizel D et al. Impaired glucose tolerance in the absence of adenosine A1 receptor signaling. Diabetes 60(10), 2578-2587 (2011).
145. Nemeth ZH, Bleich D, Csoka B et al. Adenosine receptor activation ameliorates Type 1 diabetes. FASEB J. 21(10), 2379-2388 (2007).
146. Figler RA, Wang G, Srinivasan S et al. Links between insulin resistance, adenosine A2B receptors, and inflammatory markers in mice and humans. Diabetes 60(2), 669-679 (2011).
147. Kloner RA, Forman MB, Gibbons RJ et al. Impact of time to therapy and reperfusion modality on the efficacy of adenosine in acute myocardial infarction: The AMISTAD-2 trial. Eur. Heart J. 27(20), 2400-2405 (2006).
148. Mahaffey KW, Puma JA, Barbagelata NA et al. Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: Results of a multicenter, randomized, placebo-controlled trial: The Acute Myocardial Infarction Study of Adenosine (AMISTAD) trial. J. Am. Coll. Cardiol. 34(6), 1711-1720 (1999).
149. Ross AM, Gibbons RJ, Stone GW, Kloner RA, Alexander RW. A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J. Am. Coll. Cardiol. 45(11), 1775-1780 (2005).
150. Nees S, Herzog V, Becker BF, Bock M, Des Rosier C. The coronary endothelium: A highly active metabolic barrier for adenosine. Basic Res. Cardiol. 80, 515-529 (1985).
151. Gamboa A, Ertl AC, Costa F et al. Blockade of nucleoside transport is required for delivery of intraarterial adenosine into the interstitium: Relevance to therapeutic preconditioning in humans. Circulation 108(21), 2631-2635 (2003).
152. Smits P, Boekema P, Thien T, de Abreu R, van't Laar A. Evidence for an antagonism between caffeine and adenosine in the cardiovascular system in man. J. Cardiovasc. Pharmacol. 10, 136-143 (1987).
153. Gao ZG, Kim SK, Ijzerman AP, Jacobson KA. Allosteric modulation of the adenosine family of receptors. Mini. Rev. Med. Chem. 5(6), 545-553 (2005).
154. Amoah-Apraku B, Xu J, Lu JY et al. Selective potentiation by an A1 adenosine receptor enhancer of the negative dromotropic action of adenosine in the guinea pig heart. J. Pharmacol. Exp. Ther. 266(2), 611-617 (1993).
155. Mizumura T, Auchampach JA, Linden J, Bruns RF, Gross GJ. PD 81,723, an allosteric enhancer of the A1 adenosine receptor, lowers the threshold for ischemic preconditioning in dogs. Circ. Res. 79(3), 415-423 (1996).
156. Kiesman WF, Elzein E, Zablocki J. A1 adenosine receptor antagonists, agonists, and allosteric enhancers. Handb. Exp. Pharmacol.(193), 25-58 (2009).
157. Kalinowski L, Dobrucki LW, Szczepanska-Konkel M et al. Third-generation beta-blockers stimulate nitric oxide release from endothelial cells through ATP efflux: A novel mechanism for antihypertensive action. Circulation 107(21), 2747-2752 (2003).
158. Montesinos MC, Takedachi M, Thompson LF et al. The antiinflammatory mechanism of methotrexate depends on extracellular conversion of adenine nucleotides to adenosine by ecto-5′-nucleotidase: Findings in a study of ecto-5′-nucleotidase gene-deficient mice. Arthritis Rheum. 56(5), 1440-1445 (2007).
159. Sanada S, Asanuma H, Minamino T et al. Optimal windows of statin use for immediate infarct limitation: 5′-nucleotidase as another downstream molecule of phosphatidylinositol 3-kinase. Circulation 110(15), 2143-2149 (2004).
160. Schmidt K, Tissier R, Ghaleh B et al. Cardioprotective effects of mineralocorticoid receptor antagonists at reperfusion. Eur. Heart J. 31(13), 1655-1662 (2010).
161. Meijer P, Oyen WJ, Dekker D et al. Rosuvastatin increases extracellular adenosine formation in humans in vivo: A new perspective on cardiovascular protection. Arterioscler. Thromb. Vasc. Biol. 29(6), 963-968 (2009).
162. Meijer P, Wouters CW, van den Broek PH et al. Upregulation of ecto-5′-nucleotidase by rosuvastatin increases the vasodilator response to ischemia. Hypertension 56(4), 722-727 (2010).
163. Zhang L, He H, Balschi JA. Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration. Am. J. Physiol. Heart Circ. Physiol. 293(1), H457-H466 (2007).
164. Paiva M, Riksen NP, Davidson SM et al. Metformin prevents myocardial reperfusion injury by activating the adenosine receptor. J. Cardiovasc. Pharmacol. 53(5), 373-378 (2009).
165. Meijer P, Wouters CW, van den Broek PH et al. Dipyridamole enhances ischaemia-induced reactive hyperaemia by increased adenosine receptor stimulation. Br. J. Pharmacol. 153(6), 1169-1176 (2008).
166. Rongen GA, Smits P, Ver Donck K et al. Hemodynamic and neurohumoral effects of various grades of selective adenosine transport inhibition in humans. Implications for its future role in cardioprotection. J. Clin. Invest. 95, 658-668 (1995).
167. Mailliard WS, Diamond I. Recent advances in the neurobiology of alcoholism: The role of adenosine. Pharmacol. Ther. 101(1), 39-46 (2004).
168. Riksen NP, Barrera P, van den Broek PH et al. Methotrexate modulates the kinetics of adenosine in humans in vivo. Ann. Rheum. Dis. 65(4), 465-470 (2005).
169. Riksen NP, Rongen GA, Blom HJ, Boers GH, Smits P. Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia. Clin. Chem. Lab Med. 43(10), 1001-1006 (2005).
170. Smits P, Aengevaeren WR, Corstens FH, Thien T. Caffeine reduces dipyridamole-induced myocardial ischemia. J. Nucl. Med. 30(10), 1723-1726 (1989).
171. Smits P, Corstens FH, Aengevaeren WR, Wackers FJ, Thien T. False-negative dipyridamole-thallium-201 myocardial imaging after caffeine infusion. J. Nucl. Med. 32(8), 1538-1541 (1991).
172. Johnston DL, Daley JR, Hodge DO, Hopfenspirger MR, Gibbons RJ. Hemodynamic responses and adverse effects associated with adenosine and dipyridamole pharmacologic stress testing: A comparison in 2000 patients. Mayo Clin. Proc. 70, 331-336 (1995).
173. Miyamoto MI, Clarke KA, Thomas GS, Belardinelli L. An example of the clinical selectivity of regadenoson for the A2a adenosine receptor. Am. Heart Hosp. J. 7(2), E118-E121 (2009).
174. Thomas GS, Tammelin BR, Schiffman GL et al. Safety of regadenoson, a selective adenosine A2A agonist, in patients with chronic obstructive pulmonary disease: A randomized, double-blind, placebo-controlled trial (RegCOPD trial). J. Nucl. Cardiol. 15(3), 319-328 (2008).
175. Leaker BR, O'Connor B, Hansel TT et al. Safety of regadenoson, an adenosine A2A receptor agonist for myocardial perfusion imaging, in mild asthma and moderate asthma patients: A randomized, double-blind, placebo-controlled
176. Cerqueira MD, Nguyen P, Staehr P, Underwood SR, Iskandrian AE. Effects of age, gender, obesity, and diabetes on the efficacy and safety of the selective A2A agonist regadenoson versus adenosine in myocardial perfusion imaging integrated ADVANCE-MPI trial results. JACC Cardiovasc. Imaging 1(3), 307-316 (2008).
177. Iskandrian AE, Bateman TM, Belardinelli L et al. Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: Results of the ADVANCE Phase 3 multicenter international trial. J. Nucl. Cardiol. 14(5), 645-658 (2007).
178. Grady EC, Barron JT, Wagner RH. Development of asystole requiring cardiac resuscitation after the administration of regadenoson in a patient with pulmonary fibrosis receiving n-acetylcysteine. J. Nucl. Cardiol. 18(3), 521-525 (2011).
179. Gordi T, Frohna P, Sun HL et al. A population pharmacokinetic/ pharmacodynamic analysis of regadenoson, an adenosine A2A-receptor agonist, in healthy male volunteers. Clin. Pharmacokinet. 45(12), 1201-1212 (2006).
180. Gordi T, Blackburn B, Lieu H. Regadenoson pharmacokinetics and tolerability in subjects with impaired renal function. J. Clin. Pharmacol. 47(7), 825-833 (2007).
181. Brady WJ Jr, DeBehnke DJ, Wickman LL, Lindbeck G. Treatment of out-of-hospital supraventricular tachycardia: Adenosine vs verapamil. Acad. Emerg. Med. 3, 574-585 (1996).
182. DiMarco JP, Miles W, Akhtar M et al. Adenosine for paroxysmal supraventricular tachycardia: Dose ranging and comparison with verapamil. Ann. Intern. Med. 113, 104-110 (1990).
183. Lerman BB, Ellenbogen KA, Kadish A et al. Electrophysiologic effects of a novel selective adenosine A1 agonist (CVT-510) on atrioventricular nodal conduction in humans. J. Cardiovasc Pharmacol. Ther. 6(3), 237-245 (2001).
184. Prystowsky EN, Niazi I, Curtis AB et al. Termination of paroxysmal supraventricular tachycardia by tecadenoson (CVT-510), a novel A1-adenosine receptor agonist. J. Am. Coll. Cardiol. 42(6), 1098-1102 (2003).
185. Palle VP, Varkhedkar V, Ibrahim P et al. Affinity and intrinsic efficacy (IE) of 5'-carbamoyl adenosine analogues for the A1 adenosine receptor-efforts towards the discovery of a chronic ventricular rate control agent for the treatment of atrial fibrillation (AF). Bioorg. Med. Chem. Lett. 14(2), 535-539 (2004).
186. Wu L, Belardinelli L, Zablocki JA, Palle V, Shryock JC. A partial agonist of the A(1)-adenosine receptor selectively slows AV conduction in guinea pig hearts. Am. J. Physiol. Heart Circ. Physiol. 280(1), H334-H343 (2001).
187. Nicholls SJ, Ballantyne CM, Barter PJ et al. Effect of two intensive statin regimens on progression of coronary disease. N. Engl. J. Med. 365(22), 2078-2087 (2011).
188. Wouters CW, Wever KE, Bronckers I et al. Short-term statin treatment does not prevent ischemia and reperfusion-induced endothelial dysfunction in humans. J. Cardiovasc. Pharmacol. 59(1), 22-28 (2012).
189. Van Belle H. Nucleoside transport inhibition: A therapeutic approach to cardioprotection via adenosine? Cardiovasc. Res. 27, 68-76 (1993).
190. Biaggioni I, Onrot J, Hollister AS, Robertson D. Cardiovascular effects of adenosine infusion in man and their modulation by dipyridamole. Life Sci. 39, 2229-2236 (1986).
191. Smits P, Straatman C, Pijpers E, Thien T. Dose-dependent inhibition of the hemodynamic response to dipyridamole by caffeine. Clin. Pharmacol. Ther. 50, 529-537 (1991).
192. Gamboa A, Abraham R, Diedrich A et al. Role of adenosine and nitric oxide on the mechanisms of action of dipyridamole. Stroke 36(10), 2170-2175 (2005).
193. Riksen NP, Oyen WJ, Ramakers BP et al. Oral therapy with dipyridamole limits ischemia-reperfusion injury in humans. Clin. Pharmacol. Ther. 78(1), 52-59 (2005).
194. Verro P, Gorelick PB, Nguyen D. Aspirin plus dipyridamole versus aspirin for prevention of vascular events after stroke or TIA: A meta-analysis. Stroke 39(4), 1358-1363 (2008).
195. Halkes PH, van GJ, Kappelle LJ, Koudstaal PJ, Algra A. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): Randomised controlled trial. Lancet 367(9523), 1665-1673 (2006).
196. Derendorf H, VanderMaelen CP, Brickl RS, MacGregor TR, Eisert W. Dipyridamole bioavailability in subjects with reduced gastric acidity. J. Clin. Pharmacol. 45(7), 845-850 (2005).
197. Ye Y, Lin Y, Perez-Polo R et al. Enhanced cardioprotection against ischemia-reperfusion injury with a dipyridamole and low-dose atorvastatin combination. Am. J. Physiol. Heart Circ. Physiol. 293(1), H813-H818 (2007).
198. Kinugawa T, Fujita M, Ogino K et al. Catabolism of adenine nucleotides favors adenosine production following exercise in patients with chronic heart failure. J. Card. Fail. 12(9), 720-725 (2006).
199. Asakura M, Asanuma H, Kim J et al. Impact of adenosine receptor signaling and metabolism on pathophysiology in patients with chronic heart failure. Hypertens. Res. 30(9), 781-787 (2007).
200. Fujita M, Asakura M, Sanada S et al. Activation of ecto-5′- nucleotidase in the blood and hearts of patients with chronic heart failure. J. Card Fail. 14(5), 426-430 (2008).
201. Funakoshi H, Zacharia LC, Tang Z et al. A1 adenosine receptor upregulation accompanies decreasing myocardial adenosine levels in mice with left ventricular dysfunction. Circulation 115(17), 2307-2315 (2007).
202. Del Ry S, Cabiati M, Martino A et al. Adenosine receptor mRNA expression in normal and failing minipig hearts. J. Cardiovasc. Pharmacol. 58(2), 149-156 (2011).
203. Franceschi F, Deharo JC, Giorgi R et al. Peripheral plasma adenosine release in patients with chronic heart failure. Heart 95(8), 651-655 (2009).
204. Notarius CF, Atchison DJ, Rongen GA, Floras JS. Effect of adenosine receptor blockade with caffeine on sympathetic response to handgrip exercise in heart failure. Am. J Physiol. Heart Circ. Physiol. 281(3), H1312-H1318 (2001).
205. Notarius CF, Atchison DJ, Floras JS. Impact of heart failure and exercise capacity on sympathetic response to handgrip exercise. Am. J. Physiol. Heart Circ. Physiol. 280(3), H969-H976 (2001).
206. Voors AA, Dittrich HC, Massie BM et al. Effects of the adenosine A1 receptor antagonist rolofylline on renal function in patients with acute heart failure and renal dysfunction: Results from PROTECT (Placebo-Controlled Randomized Study of the Selective Adenosine A1 Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function). J. Am. Coll. Cardiol. 57(19), 1899-1907 (2011).
207. Pang PS, Mehra M, Maggioni AP et al. Rationale, design, and results from RENO-DEFEND 1: A randomized, dose-finding study of the selective A1 adenosine antagonist SLV320 in patients hospitalized with acute heart failure. Am. Heart J. 161(6), 1012-1023 (2011).
208. Sanada S, Asanuma H, Koretsune Y et al. Long-term oral administration of dipyridamole improves both cardiac and physical status in patients with mild to moderate chronic heart failure: A prospective open-randomized study. Hypertens. Res. 30(10), 913-919 (2007).
209. Kopecky SL, Aviles RJ, Bell MR et al. A randomized, double-blinded, placebo-controlled, dose-ranging study measuring the effect of an adenosine agonist on infarct size reduction in patients undergoing primary percutaneous transluminal coronary angioplasty: The ADMIRE (AmP579 Delivery for Myocardial Infarction Reduction) study. Am. Heart J. 146(1), 146-152 (2003).
210. Desmet W, Bogaert J, Dubois C et al. High-dose intracoronary adenosine for myocardial salvage in patients with acute ST-segment elevation myocardial infarction. Eur. Heart J. 32(7), 867-877 (2011).
211. Vinten-Johansen J, Zhao ZQ, Corvera JS et al. Adenosine in myocardial protection in on-pump and off-pump cardiac surgery. Ann. Thorac. Surg. 75(2), S691-S699 (2003).
212. Roberts AJ, Jacobstein JG, Cipriano PR et al. Effectiveness of dipyridamole in reducing the size of experimental myocardial infarction. Circulation 61(2), 228-236 (1980).
213. Matsuoka H, Henrichs KJ, Schaper W. Influence of dipyridamole on infarct size and on cardiac nucleoside content following coronary occlusion in the dog. Basic Res. Cardiol. 80(6), 682-692 (1985).
214. Mangano DT, Miao Y, Tudor IC, Dietzel C. Post-reperfusion myocardial infarction: long-term survival improvement using adenosine regulation with acadesine. J. Am. Coll. Cardiol. 48(1), 206-214 (2006).
215. Asanuma H, Sanada S, Ogai A et al. Methotrexate and MX-68, a new derivative of methotrexate, limit infarct size via adenosine-dependent mechanisms in canine hearts. J. Cardiovasc. Pharmacol. 43(4), 574-579 (2004).
216. Patti G, Pasceri V, Colonna G et al. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: Results of the ARMYDA-ACS randomized trial. J. Am. Coll. Cardiol. 49(12), 1272-1278 (2007).
217. El Messaoudi SE, Rongen GA, de Boer RA, Riksen NP. The cardioprotective effects of metformin. Curr. Opin. Lipidol. 22(6), 445-453 (2011).
218. Mills JH, Alabanza L, Weksler BB et al. Human brain endothelial cells are responsive to adenosine receptor activation. Purinergic. Signal. 7(2), 265-273 (2011).
219. Ngamsri KC, Wagner R, Vollmer I, Stark S, Reutershan J. Adenosine receptor A1 regulates polymorphonuclear cell trafficking and microvascular permeability in lipopolysaccharide-induced lung injury. J. Immunol. 185(7), 4374-4384 (2010).
220. Clark AN, Youkey R, Liu X et al. A1 adenosine receptor activation promotes angiogenesis and release of VEGF from monocytes. Circ. Res. 101(11), 1130-1138 (2007).
221. Thakur S, Du J, Hourani S, Ledent C, Li JM. Inactivation of adenosine A2A receptor attenuates basal and angiotensin II-induced ROS production by Nox2 in endothelial cells. J. Biol. Chem. 285(51), 40104-40113 (2010).
222. Umapathy NS, Fan Z, Zemskov EA et al. Molecular mechanisms involved in adenosine-induced endothelial cell barrier enhancement. Vascul. Pharmacol. 52(5-6), 199-206 (2010).
223. Wen J, Grenz A, Zhang Y et al. A2B adenosine receptor contributes to penile erection via PI3K/AKT signaling cascade-mediated eNOS activation. FASEB J. 25(8), 2823-2830 (2011).
224. Ansari HR, Nadeem A, Talukder MA, Sakhalkar S, Mustafa SJ. Evidence for the involvement of nitric oxide in A2B receptor-mediated vasorelaxation of mouse aorta. Am. J. Physiol. Heart Circ. Physiol. 292(1), H719-H725 (2007).
225. Dubey RK, Gillespie DG, Jackson EK. A(2B) adenosine receptors stimulate growth of porcine and rat arterial endothelial cells. Hypertension 39(2 Pt 2), 530-535 (2002).
226. Wagner R, Ngamsri KC, Stark S, Vollmer I, Reutershan J. Adenosine receptor A3 is a critical mediator in LPS-induced pulmonary inflammation. Am. J. Physiol. Lung Cell Mol. Physiol. 299(4), L502-L512 (2010).
227. Ansari HR, Nadeem A, Tilley SL, Mustafa SJ. Involvement of COX-1 in A3 adenosine receptor-mediated contraction through endothelium in mice aorta. Am. J. Physiol. Heart Circ. Physiol. 293(6), H3448-H3455 (2007).
228. Leal S, Sa C, Goncalves J, Fresco P, Diniz C. Immunohistochemical characterization of adenosine receptors in rat aorta and tail arteries. Microsc. Res. Tech. 71(10), 703-709 (2008).
229. Shen J, Halenda SP, Sturek M, Wilden PA. Cell-signaling evidence for adenosine stimulation of coronary smooth muscle proliferation via the A1 adenosine receptor. Circ. Res. 97(6), 574-582 (2005).
230. Tawfik HE, Schnermann J, Oldenburg PJ, Mustafa SJ. Role of A1 adenosine receptors in regulation of vascular tone. Am. J. Physiol. Heart Circ. Physiol. 288(3), H1411-H1416 (2005).
231. Just A and Arendshorst WJ. A novel mechanism of renal blood flow autoregulation and the autoregulatory role of A1 adenosine receptors in mice. Am. J. Physiol. Renal Physiol. 293(5), F1489-F1500 (2007).
232. Ansari HR, Teng B, Nadeem A et al. A(1) adenosine receptor-mediated PKC and p42/p44 MAPK signaling in mouse coronary artery smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 297(3), H1032-H1039 (2009).
233. El-Awady MS, Ansari HR, Fil D, Tilley SL, Mustafa SJ. NADPH oxidase pathway is involved in aortic contraction induced by A3 adenosine receptor in mice. J. Pharmacol. Exp. Ther. 338(2), 711-717 (2011).
234. Diniz C, Fresco P, Leal S, Goncalves J. Adenosine receptors involved in modulation of noradrenaline release in isolated rat tail artery. Eur. J. Pharmacol. 504(1-2), 17-25 (2004).
235. Bott-Flugel L, Bernshausen A, Schneider H et al. Selective attenuation of norepinephrine release and stress-induced heart rate increase by partial adenosine A1 agonism. PLoS. One 6(3), e18048(2011).
236. Fresco P, Diniz C, Goncalves J. Facilitation of noradrenaline release by activation of adenosine A(2A) receptors triggers both phospholipase C and adenylate cyclase pathways in rat tail artery. Cardiovasc. Res. 63(4), 739-746 (2004).
237. Middlekauff HR, Rivkees SA, Raybould HE et al. Localization and functional effects of adenosine A1 receptors on cardiac vagal afferents in adult rats. Am. J. Physiol. 274(2 Pt 2), H441-H447 (1998).
238. Chuaychoo B, Lee MG, Kollarik M, Pullmann R Jr, Undem BJ. Evidence for both adenosine A1 and A2A receptors activating single vagal sensory C-fibres in guinea pig lungs. J. Physiol. 575(Pt 2), 481-490 (2006).
239. Dibner-Dunlap ME, Kinugawa T, Thames MD. Activation of cardiac sympathetic afferents - effects of exogenous adenosine and adenosine analogues. Am. J. Physiol. 265, H395-H400 (1993).
240. Kirkup AJ, Eastwood C, Grundy D, Chessell IP, Humphrey PP. Characterization of adenosine receptors evoking excitation of mesenteric afferents in the rat. Br. J. Pharmacol. 125(6), 1352-1360 (1998).
241. Costa F, Biaggioni I. Adenosine activates afferent fibers in the forearm, producing sympathetic stimulation in humans. J. Pharmacol. Exp. Ther. 267, 1369-1374 (1993).
242. Costa F, Diedrich A, Johnson B et al. Adenosine, a metabolic trigger of the exercise pressor reflex in humans. Hypertension 37(3), 917-922 (2001).
243. Gauda EB, Northington FJ, Linden J, Rosin DL. Differential expression of a(2a), A(1)-adenosine and D(2)-dopamine receptor genes in rat peripheral arterial chemoreceptors during postnatal development. Brain Res. 872(1-2), 1-10 (2000).
244. Chandrasekera PC, McIntosh VJ, Cao FX, Lasley RD. Differential effects of adenosine A2a and A2b receptors on cardiac contractility. Am. J. Physiol. Heart Circ. Physiol. 299(6), H2082-H2089 (2010).
245. Lankford AR, Yang JN, Rose'Meyer R et al. Effect of modulating cardiac A1 adenosine receptor expression on protection with ischemic preconditioning. Am. J. Physiol. Heart Circ. Physiol. 290(4), H1469-H1473 (2006).
246. Zhan E, McIntosh VJ, Lasley RD. Adenosine AA and AB receptors are both required for adenosine A receptor-mediated cardioprotection. Am. J. Physiol. Heart Circ. Physiol. 301(3), H1183-H1189 (2011).
247. Du L, Gao ZG, Nithipatikom K et al. Protection from myocardial ischemia/reperfusion injury by a positive allosteric modulator of the a3 adenosine receptor. J. Pharmacol. Exp. Ther. 340(1), 210-217 (2012).
248. Cerniway RJ, Yang Z, Jacobson MA, Linden J, Matherne GP. Targeted deletion of A(3) adenosine receptors improves tolerance to ischemia-reperfusion injury in mouse myocardium. Am. J. Physiol. Heart Circ. Physiol. 281(4), H1751-H1758 (2001).
249. Meester BJ, Shankley NP, Welsh NJ et al. Pharmacological classification of adenosine receptors in the sinoatrial and atrioventricular nodes of the guinea-pig. Br. J. Pharmacol. 124(4), 685-692 (1998).
250. Kirchhof P, Fabritz L, Fortmuller L et al. Altered sinus nodal and atrioventricular nodal function in freely moving mice overexpressing the A1 adenosine receptor. Am. J. Physiol. Heart Circ. Physiol. 285(1), H145-H153 (2003).