Delayed or second window preconditioning induced by adenosine al receptor activation is independent of early generation of nitric oxide or late induction of inducible nitric oxide synthase.
J CARDIOVASC PHARM
278 - 287.
Transient adenosine A(1) receptor (A(1)R) activation induces a second window or delayed preconditioning against myocardial infarction 24-72 h later. Early generation of nitric oxide and delayed induction of nitric oxide synthase have been implicated in mediating delayed cardioprotection after ischemic preconditioning in rabbits. Recent evidence indicates that some of the regulatory roles of adenosine in cardiac tissue may be mediated by A,R-induced generation of nitric oxide. This study examined the role of nitric oxide in the mediation of A,R-induced delayed preconditioning against infarction. Pharmacologic preconditioning of rabbits with the selective A(1)R agonist 2-chloro-N-6-cyclopentyladenosine 100 mug/kg (CCPA) significantly reduced myocardial infarct size compared with control animals, after 30 min regional ischemia and 2 h reperfusion in vivo 24 h later (27.3 +/-4.7 vs. 46.0 +/-3.7%, respectively: p = 0.001). Nonselective inhibition of nitric oxide synthase with N-G-nitro-L-arginine methyl ester(10 mg/kg) before administration of CCPA did not affect this infarct limitation at 24 h. Selective inhibition of inducible nitric oxide synthase before the prolonged ischemic insult on day 2, with two structurally independent inducible nitric oxide synthase inhibitors, L-N-6-(1-iminoethyl)-lysine (10 mg/kg) or aminoguanidine (300 mg/kg), did not abrogate the reduction in infarction observed by pharmacologic preconditioning with CCPA 24 h earlier. These results suggest that the second window or delayed protection against myocardial infarction observed 24 h after pharmacologic preconditioning with an adenosine A, agonist occurs independently of either early generation of nitric oxide or subacute induction of inducible nitric oxide synthase.
|Title:||Delayed or second window preconditioning induced by adenosine al receptor activation is independent of early generation of nitric oxide or late induction of inducible nitric oxide synthase|
|Keywords:||adenosine, myocardial infarction, delayed preconditioning, nitric oxide, PROTEIN-KINASE-C, MONOPHOSPHORYL-LIPID-A, ATRIOVENTRICULAR NODAL CELLS, GENE-KNOCKOUT MICE, CONSCIOUS RABBITS, MYOCARDIAL PROTECTION, A(1) RECEPTOR, LATE-PHASE, BRIEF ISCHEMIA, IN-VIVO|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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