Cardiovascular Research

ATL 313, A Selective A(2A) Adenosine Receptor Agonist, Reduces Myocardial Infarct Size in a Rat Ischemia/Reperfusion Model.

Authors: Wangde Dai|||Sharon L Hale|||Rohith Nayak|||Robert A Kloner

Affiliations: + Expand

Abstract

The cardioprotective effects of activation of the A(2A) adenosine receptor (A(2A)AR) on ischemia/reperfusion injury in the heart remain controversial. We investigated whether ATL 313, a new selective A(2A)AR agonist, could reduce myocardial infarct size in a rat ischemia/reperfusion model.

---

Reference List

Kloner RA, Forman MB, Gibbons RJ, Ross AM, Alexander RW, Stone GW. Impact of time to therapy and reperfusion modality on the efficacy of adenosine in acute myocardial infarction: the AMISTAD-2 trial. Eur Heart J. 2006;27:2400–5.|||Hale Sl, Bellows SD, Hammerman H, Kloner RA. An adenosine A1 receptor agonist, R(-)-N-(2-phenylisopropyl)-adenosine (PIA), but not adenosine itself, acts as a therapeutic preconditioningmimetic agent in rabbits. Cardiovasc Res. 1993;27:2140–5.|||Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J. International union of pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev. 2001;53:527–52.|||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. 2001;280:H1660–6.|||Glover DK, Riou LK, Ruiz M, et al. Reduction of infarct size and postischemic inflammation from ATL-146e, a highly selective adenosine A2A receptor agonist, in reperfused canine myocardium. Am J Physiol Heart Circ Physiol. 2005;288:H1851–8.|||Thornton JD, Liu GS, Olsson RA, Downey JM. Intravenous pretreatment with A1-selective adenosine analogues protects the heart against infarction. Circulation. 1992;85:659–65.|||Lasley RD, Kristo G, Keith BJ, Mentzer RM Jr. The A2a/A2b receptor antagonist ZM-241385 blocks the cardioprotective effect of adenosine agonist pretreatment in in vivo rat myocardium. Am J Physiol Heart Circ Physiol. 2007;292:h426–31.|||Rivo J, Zeira E, Galun E, Einav S, Linden J, Matot I. Attenuation of reperfusion lung injury and apoptosis by A2A adenosine receptor activation is associated with modulation of Bcl-2 and Bax expression and activation of extracellular signal-regulated kinases. Shock. 2007;27:266–73.|||Gazoni LM, Laubach VE, Mulloy DP, et al. Additive protection against lung ischemia-reperfusion injury by adenosine A2A receptor activation before procurement and during reperfusion. J Thorac Cardiovasc Surg. 2008;135:156–65.|||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. 1997;280:301–9.|||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. 2005;111:2190–7.|||Smits GJ, McVey M, Cox BF, Perrone MH, Clark KL. Cardioprotective effects of the novel adenosine A1/A2 receptor agonist AMP 579 in a porcine model of myocardial infarction. J Pharmacol Exp Ther. 1998;286:611–8.|||Marala RB, Mustafa SJ. Immunological characterization of adenosine A2A receptors in human and porcine cardiovascular tissues. J Pharmacol Exp Ther. 1998;286:1051–7.|||Dobson JG Jr, Fenton RA. Adenosine A2 receptor function in rat ventricular myocytes. Cardiovasc Res. 1997;34:337–47.|||Kilpatrick EL, Narayan P, Mentzer RM Jr, Lasley RD. Cardiac myocyte adenosine A2a receptor activation fails to alter cAMP or contractility: role of receptor localization. Am J Physiol Heart Circ Physiol. 2002;282:H1035–40.|||Ramagopal MV, Chitwood RW Jr, Mustafa SJ, et al. Evidence for an A2 adenosine receptor in human coronary arteries. Eur J Pharmacol. 1988;151:483–6.|||Kloner RA, Przylenk K, Whittaker P, Hale S. Preconditioning stimuli and inadvertent preconditioning. J Mol Cell Cardiol. 1995;27:743–7.|||Sun WC, Moore JN, Hurley DJ, Vandenplas ML, Linden JM, Murray TF. Pharmacologic characterization of novel adenosine A2A receptor agonists in equine neutrophils. Am J Vet Res. 2007;68:981–7.