© 2001 American Heart Association, Inc.
Integrative Physiology |
A1 or A3 Adenosine Receptors Induce Late Preconditioning Against Infarction in Conscious Rabbits by Different Mechanisms
From the Division of Cardiology (H.T., R.B., R.G.B., E.K., X.-L.T., Z.Y., J.A.A.), University of Louisville and Jewish Heart and Lung Institute, Louisville, Ky; Department of Microbiology (S.B.), Columbia University, New York, NY.
Correspondence to John A. Auchampach, PhD, Department of Pharmacology, 8701 Watertown Plank Road, Medical College of Wisconsin, Milwaukee, WI 53226. E-mail jauchamp{at}mcw.edu
Abstract—We
investigated whether activation of A1 or
A3 adenosine receptors (ARs) induces late
preconditioning (PC) against infarction in conscious rabbits using the
selective AR agonists
2-chloro-N6-cyclopentyladenosine
(CCPA) and
N6-3-iodobenzyladenosine-5'-N-methylcarboxamide
(IB-MECA). In vitro radioligand binding and cAMP assays demonstrated
CCPA to be 
200- to 400-fold selective for the rabbit
A1AR and IB-MECA to be 20-fold selective for
the rabbit A3AR. We observed that (1)
pretreatment of rabbits 24 hours earlier with CCPA (100 µg/kg IV
bolus) or IB-MECA (100 or 300 µg/kg) resulted in an 35% to 40%
reduction in the size of the infarct induced by 30 minutes of coronary
artery occlusion and 72 hours of reperfusion compared with
vehicle-treated rabbits, whereas pretreatment with the selective
A2AAR agonist CGS 21680 (100 µg/kg) had no
effect; (2) the delayed cardioprotective effect of CCPA, but not that
of IB-MECA, was completely blocked by coadministration of the highly
selective A1AR antagonist N-0861; (3) inhibition
of nitric oxide synthase (NOS) with
N
-nitro-L-arginine
during the 30-minute occlusion abrogated the infarct-sparing action of
CCPA but not that of IB-MECA; and (4) inhibition of ATP-sensitive
potassium (KATP) channels with sodium
5-hydroxydecanoate during the 30-minute occlusion blocked the
cardioprotective effects of both CCPA and IB-MECA. Taken together,
these results indicate that activation of either
A1ARs or A3ARs (but not
A2AARs) elicits delayed protection against
infarction in conscious rabbits and that both
A1AR- and A3AR-induced
cardioprotection involves opening of KATP
channels. However, A1AR-induced late PC uses an
NOS-dependent pathway whereas A3AR-induced late
PC is mediated by an NOS-independent
pathway.
Key Words: adenosine receptors • ischemia/reperfusion injury • myocardial infarction • ATP-dependent potassium channels • nitric oxide synthase
This article has been cited by other articles:
 |
|
 |
|
  T. C. Wan, Z.-D. Ge, A. Tampo, Y. Mio, M. W. Bienengraeber, W. R. Tracey, G. J. Gross, W.-M. Kwok, and J. A. Auchampach The A3 Adenosine Receptor Agonist CP-532,903 [N6-(2,5-Dichlorobenzyl)-3'-aminoadenosine-5'-N-methylcarboxamide] Protects against Myocardial Ischemia/Reperfusion Injury via the Sarcolemmal ATP-Sensitive Potassium Channel J. Pharmacol. Exp. Ther., January 1, 2008; 324(1): 234 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Brown and R. L. Moore Perspectives in innate and acquired cardioprotection: cardioprotection acquired through exercise J Appl Physiol, November 1, 2007; 103(5): 1894 - 1899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-D. Ge, J. N. Peart, L. M. Kreckler, T. C. Wan, M. A. Jacobson, G. J. Gross, and J. A. Auchampach Cl-IB-MECA [2-Chloro-N6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide] Reduces Ischemia/Reperfusion Injury in Mice by Activating the A Adenosine Receptor J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1200 - 1210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Couvreur, L. Lucats, R. Tissier, A. Bize, A. Berdeaux, and B. Ghaleh Differential effects of postconditioning on myocardial stunning and infarction: a study in conscious dogs and anesthetized rabbits Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1345 - H1350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-S. Park, H. Zhao, Y. Jang, R. A. Mueller, and Z. Xu N6-(3-Iodobenzyl)-adenosine-5'-N-methylcarboxamide Confers Cardioprotection at Reperfusion by Inhibiting Mitochondrial Permeability Transition Pore Opening via Glycogen Synthase Kinase 3beta J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 124 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Brown, A. J. Chicco, K. N. Jew, M. S. Johnson, J. M. Lynch, P. A. Watson, and R. L. Moore Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the rat J. Physiol., December 15, 2005; 569(3): 913 - 924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Guo, A. B. Stein, W.-J. Wu, X. Zhu, W. Tan, Q. Li, and R. Bolli Late preconditioning induced by NO donors, adenosine A1 receptor agonists, and {delta}1-opioid receptor agonists is mediated by iNOS Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2251 - H2257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kher, K. K. Meldrum, M. Wang, B. M. Tsai, J. M. Pitcher, and D. R. Meldrum Cellular and molecular mechanisms of sex differences in renal ischemia-reperfusion injury Cardiovasc Res, September 1, 2005; 67(4): 594 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Lasley, B. J. Keith, G. Kristo, Y. Yoshimura, and R. M. Mentzer Jr. Delayed adenosine A1 receptor preconditioning in rat myocardium is MAPK dependent but iNOS independent Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H785 - H791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhang, D. E. Handy, and J. Loscalzo Adenosine-Dependent Induction of Glutathione Peroxidase 1 in Human Primary Endothelial Cells and Protection Against Oxidative Stress Circ. Res., April 29, 2005; 96(8): 831 - 837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Stein, X.-L. Tang, Y. Guo, Y.-T. Xuan, B. Dawn, and R. Bolli Delayed Adaptation of the Heart to Stress: Late Preconditioning Stroke, November 1, 2004; 35(11_suppl_1): 2676 - 2679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-L. Tang, Y.-T. Xuan, Y. Zhu, G. Shirk, and R. Bolli Nicorandil induces late preconditioning against myocardial infarction in conscious rabbits Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1273 - H1280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. YELLON and J. M. DOWNEY Preconditioning the Myocardium: From Cellular Physiology to Clinical Cardiology Physiol Rev, October 1, 2003; 83(4): 1113 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Auchampach, Z.-D. Ge, T. C. Wan, J. Moore, and G. J. Gross A3 adenosine receptor agonist IB-MECA reduces myocardial ischemia-reperfusion injury in dogs Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H607 - H613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Zhao and R. C. Kukreja Protein kinase C-{delta} mediates adenosine A3 receptor-induced delayed cardioprotection in mouse Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H434 - H441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Peart and G. J. Gross Adenosine and opioid receptor-mediated cardioprotection in the rat: evidence for cross-talk between receptors Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H81 - H89. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fan, W. Qin, and S. J. Mustafa Characterization of adenosine receptor(s) involved in adenosine-induced bronchoconstriction in an allergic mouse model Am J Physiol Lung Cell Mol Physiol, June 1, 2003; 284(6): L1012 - L1019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Peart and J. P Headrick Adenosine-mediated early preconditioning in mouse: protective signaling and concentration dependent effects Cardiovasc Res, June 1, 2003; 58(3): 589 - 601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Li, Y. Guo, Y.-T. Xuan, C. J. Lowenstein, S. C. Stevenson, S. D. Prabhu, W.-J. Wu, Y. Zhu, and R. Bolli Gene Therapy With Inducible Nitric Oxide Synthase Protects Against Myocardial Infarction via a Cyclooxygenase-2-Dependent Mechanism Circ. Res., April 18, 2003; 92(7): 741 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-L. Tang, E. Kodani, H. Takano, M. Hill, K. Shinmura, T. M. Vondriska, P. Ping, and R. Bolli Protein tyrosine kinase signaling is necessary for NO donor-induced late preconditioning against myocardial stunning Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1441 - H1448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Peart, L. Willems, and J. P. Headrick Receptor and non-receptor-dependent mechanisms of cardioprotection with adenosine Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H519 - H527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Mentzer Jr., M. S. Jahania, and R. D. Lasley Myocardial Protection Card. Surg. Adult, January 1, 2003; 2(2003): 413 - 438. [Full Text]
|
|
|
|
|
|
E. Kodani, Y.-T. Xuan, K. Shinmura, H. Takano, X.-L. Tang, and R. Bolli delta -Opioid receptor-induced late preconditioning is mediated by cyclooxygenase-2 in conscious rabbits Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1943 - H1957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. R. Cross, E. Murphy, R. G. Black, J. Auchampach, and C. Steenbergen Overexpression of A3 adenosine receptors decreases heart rate, preserves energetics, and protects ischemic hearts Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1562 - H1568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ockaili, F. Salloum, J. Hawkins, and R. C. Kukreja Sildenafil (Viagra) induces powerful cardioprotective effect via opening of mitochondrial KATP channels in rabbits Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1263 - H1269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.F Baxter Role of adenosine in delayed preconditioning of myocardium Cardiovasc Res, August 15, 2002; 55(3): 483 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bolli, K. Shinmura, X.-L. Tang, E. Kodani, Y.-T. Xuan, Y. Guo, and B. Dawn Discovery of a new function of cyclooxygenase (COX)-2: COX-2 is a cardioprotective protein that alleviates ischemia/reperfusion injury and mediates the late phase of preconditioning Cardiovasc Res, August 15, 2002; 55(3): 506 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M Fryer, J. A Auchampach, and G. J Gross Therapeutic receptor targets of ischemic preconditioning Cardiovasc Res, August 15, 2002; 55(3): 520 - 525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Dawn, H. Takano, X.-L. Tang, E. Kodani, S. Banerjee, A. Rezazadeh, Y. Qiu, and R. Bolli Role of Src protein tyrosine kinases in late preconditioning against myocardial infarction Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H549 - H556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. Black Jr, Y. Guo, Z.-D. Ge, S. S. Murphree, S. D. Prabhu, W. K. Jones, R. Bolli, and J. A. Auchampach Gene Dosage-Dependent Effects of Cardiac-Specific Overexpression of the A3 Adenosine Receptor Circ. Res., July 26, 2002; 91(2): 165 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kudo, Y. Wang, M. Xu, A. Ayub, and M. Ashraf Adenosine A1 receptor mediates late preconditioning via activation of PKC-delta signaling pathway Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H296 - H301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Tissier, R. Souktani, P. Bruneval, J.-F. Giudicelli, A. Berdeaux, and B. Ghaleh Adenosine A1-receptor induced late preconditioning and myocardial infarction: reperfusion duration is critical Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H38 - H43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Kloner and R. B. Jennings Consequences of Brief Ischemia: Stunning, Preconditioning, and Their Clinical Implications: Part 2 Circulation, December 18, 2001; 104(25): 3158 - 3167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Kodani, K. Shinmura, Y.-T. Xuan, H. Takano, J. A. Auchampach, X.-L. Tang, and R. Bolli Cyclooxygenase-2 does not mediate late preconditioning induced by activation of adenosine A1 or A3 receptors Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H959 - H968. [Abstract] [Full Text] [PDF]
|
|