Adenosine A(1) receptor activation induces delayed preconditioning in rats mediated by manganese superoxide dismutase.
2841 - 2848.
Background-We have previously described a second window of protection against infarction in rabbits 24 to 72 hours after adenosine A, receptor (A(1)R) activation. In this study, we examined the potential role of the mitochondrial antioxidant manganese superoxide dismutase (Mn-SOD) as a potential end effector in mediating this protection.Methods and Results-Rats were treated with an intravenous bolus of the AIR agonist 2-chloro-N-6-cyclopentyladenosine (CCPA, 75 mu g/kg) or saline vehicle. They were also given a 5 mg/kg IV infusion of a 22-mer phosphorothioate oligodeoxynucleotide (ODN) with sequence antisense to the initiation site of rat Mn-SOD mRNA. Sense ODN and scrambled ODN were used as controls. Twenty-four hours later, hearts were isolated and perfused with buffer at constant pressure and subjected to 35 minutes of regional ischemia and 2 hours of reperfusion. Treatment with CCPA compared with saline vehicle (control) significantly reduced infarct size, expressed as percentage of myocardium at risk (22.3+/-3.3% versus 42.1+/-3.8%, respectively; P=0.001). This protection was completely abolished by prior treatment with antisense ODN, which had no effect on its own. Neither sense ODN nor scrambled ODN had an effect on the CCPA-induced delayed cardioprotection. In separate animals, 24 hours after the same treatment, hearts were assayed for Mn-SOD content and activity. CCPA treatment induced a significant increase in myocardial Mn-SOD content and activity compared with the control condition; this increase was abolished by pretreatment with antisense ODN.Conclusions-This is the first study to show that transient A(1)R activation induces delayed cardioprotection in the rat. These results strongly suggest an important role for mitochondrial Mn-SOD as a potential end effector of this protection.
|Title:||Adenosine A(1) receptor activation induces delayed preconditioning in rats mediated by manganese superoxide dismutase|
|Keywords:||adenosine, myocardial infarction, superoxide dismutase, TUMOR-NECROSIS-FACTOR, ISCHEMIA-REPERFUSION INJURY, PROTEIN-KINASE-C, SENSITIVE K+ CHANNELS, MYOCARDIAL PROTECTION, RABBIT HEART, 2ND WINDOW, ISCHEMIA/REPERFUSION INJURY, BIPHASIC CARDIOPROTECTION, SUBLETHAL ISCHEMIA|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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