939-77 Cellular Mechanisms for Alpha1-adrenoceptormediated Cardioprotection: Role of Protein Kinase C and Ecto-5’-Nucleotidase in Ischemic Preconditioning

It is reported that alpha1-adrenoceptor stimulation triggers the infarct size (IS)-limiting effect of ischemic preconditioning, however, its cellular mechanism is unknown. We tested the hypothesis that activation of protein kinase C (PKC) is responsible for the IS-limiting effect due to alpha1-adrenoceptor activation. In 33 open chest dogs, methoxamine (40μg/kg/min) was administered for 4 times of 5 min into the left anterior descending coronary artery with and without GF109203X, an inhibitor of PKC. IS due to 90 min of ischemia followed by 6 hrs of reperfusion in the methoxamine group was smaller than the control (IS:5±3 vs 39±7%, p<0.01). The IS-limiting effect of methoxamine was blunted by GF109203X (IS:43±3%). Methoxamine increased the activity of PKC by 213±23%, and ecto-5’-nucleotidase which converts 5’-AM P to adenosine by 78±11%. Activation of PKC and ecto-5’-nucleotidase were attenuated by GF109203X. The IS-limiting effect of methoxamine was blunted by AOPCP. an inhibitor of ecto-5’-nucleotidase (IS:37±4%). Furthermore, IS-limiting effect due to 4 times 5 min of transient coronary occlusion was blunted by GF109203X and AOPCP Thus, we conclude that activation of PKC due to alpha1-adrenoceptor stimulation limits infarct size through activation of ecto-5’-nucleotidase in ischemic preconditioning