Pharmacological preconditioning with resveratrol: role of CREB-dependent Bcl-2 signaling via adenosine A3 receptor activation

Recent studies demonstrated that resveratrol, a grape-derived polyphenolic phytoalexin, provides pharmacological preconditioning (PC) of the heart through a NO-dependent mechanism. Because adenosine receptors play a role in PC, we examined whether they play any role in resveratrol PC. Rats were randomly assigned to groups perfused for 15 min with 1) Krebs-Henseleit bicarbonate buffer (KHB) only; 2) KHB containing 10 μM resveratrol; 3) 10 μM resveratrol + 1 μM 8-cyclopentyl-1,3-dimethylxanthine (CPT; adenosine A1 receptor blocker); 4) 10 μM resveratrol + 1 μM 8-(3-chlorostyryl)caffeine (CSC; adenosine A2a receptor blocker); 5) 10 μM resveratrol + 1 μM 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191; adenosine A3 receptor blocker); or 6) 10 μM resveratrol + 3 μM 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride [LY-294002, phosphatidylinositol (PI)3-kinase inhibitor], and groups perfused with adenosine receptor blockers alone. Hearts were ...