OBJECTIVE: Ischemic postconditioning protects the reperfused heart from infarction, and this protection is dependent on the occupancy of adenosine receptors. We further explored the role of adenosine receptors in this salvage. METHODS: In situ rabbit hearts underwent 30 min of regional ischemia and 3 h of reperfusion, and postconditioning was effected with four cycles of 30-s reperfusion/30-s coronary artery occlusion at the end of ischemia. RESULTS: Postconditioning reduced infarct size from 40.2+/-3.4% of the risk zone in untreated hearts to 15.5+/-2.5%. Protection by postconditioning was blocked by either the non-selective adenosine receptor blocker 8-p-(sulfophenyl)theophylline or the A2b-selective antagonist MRS 1754, injected intravenously 5 min before reperfusion. The protein kinase C (PKC) antagonist chelerythrine also aborted postconditioning's salvage, indicating a PKC-dependent mechanism. Neither the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine nor the A2a-selective antagonist 8-(13-chlorostyryl)caffeine had an effect on protection. The non-selective but A2b-potent adenosine agonist 5'-(N-ethylcarboxamido)adenosine (NECA) infused from 5 min before to 1h after reperfusion mimicked postconditioning's effect on infarct size (17.2+/-2.7% infarction) and MRS 1754 blocked the NECA-induced cardioprotection, confirming that A2b activation was protective. The PKC activator phorbol 12-myristate 13-acetate delivered just before reperfusion also duplicated the protective effect of postconditioning (16.3+/-4.1% infarction), and co-administration of the PKC antagonist chelerythrine aborted PMA's protection, confirming that the protection was the result of PKC activation. NECA's protective effect was not affected by chelerythrine, but rather MRS 1754 blocked PMA's salutary effect (42.8+/-1.0% infarction), suggesting that the A2b receptor's effect is under control of PKC. Finally, wortmannin, a blocker of phosphatidylinositol 3-kinase, also abrogated protection by PMA. CONCLUSIONS: Salvage of ischemic myocardium by postconditioning is dependent on activation of A2b receptors, which in turn depends on activation of PKC. It is still unclear why PKC activation is required to make the heart's adenosine become protective.
OBJECTIVE:Ischemic postconditioning protects the reperfused heart from infarction, and this protection is dependent on the occupancy of adenosine receptors. We further explored the role of adenosine receptors in this salvage. METHODS: In situ rabbit hearts underwent 30 min of regional ischemia and 3 h of reperfusion, and postconditioning was effected with four cycles of 30-s reperfusion/30-s coronary artery occlusion at the end of ischemia. RESULTS: Postconditioning reduced infarct size from 40.2+/-3.4% of the risk zone in untreated hearts to 15.5+/-2.5%. Protection by postconditioning was blocked by either the non-selective adenosine receptor blocker 8-p-(sulfophenyl)theophylline or the A2b-selective antagonist MRS 1754, injected intravenously 5 min before reperfusion. The protein kinase C (PKC) antagonist chelerythrine also aborted postconditioning's salvage, indicating a PKC-dependent mechanism. Neither the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine nor the A2a-selective antagonist 8-(13-chlorostyryl)caffeine had an effect on protection. The non-selective but A2b-potent adenosine agonist 5'-(N-ethylcarboxamido)adenosine (NECA) infused from 5 min before to 1h after reperfusion mimicked postconditioning's effect on infarct size (17.2+/-2.7% infarction) and MRS 1754 blocked the NECA-induced cardioprotection, confirming that A2b activation was protective. The PKC activator phorbol 12-myristate 13-acetate delivered just before reperfusion also duplicated the protective effect of postconditioning (16.3+/-4.1% infarction), and co-administration of the PKC antagonist chelerythrine aborted PMA's protection, confirming that the protection was the result of PKC activation. NECA's protective effect was not affected by chelerythrine, but rather MRS 1754 blocked PMA's salutary effect (42.8+/-1.0% infarction), suggesting that the A2b receptor's effect is under control of PKC. Finally, wortmannin, a blocker of phosphatidylinositol 3-kinase, also abrogated protection by PMA. CONCLUSIONS: Salvage of ischemic myocardium by postconditioning is dependent on activation of A2b receptors, which in turn depends on activation of PKC. It is still unclear why PKC activation is required to make the heart's adenosine become protective.
Authors: Ming Cai; Zachary M Huttinger; Heng He; Weizhi Zhang; Feng Li; Lauren A Goodman; Debra G Wheeler; Lawrence J Druhan; Jay L Zweier; Karen M Dwyer; Guanglong He; Anthony J F d'Apice; Simon C Robson; Peter J Cowan; Richard J Gumina Journal: J Mol Cell Cardiol Date: 2011-09-12 Impact factor: 5.000
Authors: Magdalena Juhaszova; Dmitry B Zorov; Yael Yaniv; H Bradley Nuss; Su Wang; Steven J Sollott Journal: Circ Res Date: 2009-06-05 Impact factor: 17.367
Authors: Yanping Liu; Xi-Ming Yang; Efstathios K Iliodromitis; Dimitrios T Kremastinos; Turhan Dost; Michael V Cohen; James M Downey Journal: Basic Res Cardiol Date: 2007-11-12 Impact factor: 17.165