(Circulation. 1996;93:781-791.)
© 1996 American Heart Association, Inc.
Articles |
Role of Activation of Protein Kinase C in the Infarct SizeLimiting Effect of Ischemic Preconditioning Through Activation of Ecto-5'-nucleotidase
From The First Department of Medicine, Osaka (Japan) University School of Medicine; Tokai University School of Medicine (Y.S., M.C., H.M.), Department of Physiology, Isehara (Japan); and Department of Information Science (M.I.), Osaka (Japan) University Hospital.
Correspondence to Masafumi Kitakaze, MD, PhD, The First Department of Medicine, Osaka University School of Medicine, 2-2 Yamadaoka, Suita 565, Japan.
Background We have reported previously that ischemic preconditioning limits infarct size by increasing ecto-5'-nucleotidase activity. Since we have also reported that protein kinase C activation increases ecto-5'-nucleotidase activity in rat cardiomyocytes, we tested whether activation of protein kinase C during ischemic preconditioning contributes to the infarct size–limiting effect through augmentation of ecto-5'-nucleotidase activity in the canine heart.
Methods and Results The coronary artery was occluded four times for 5 minutes with alternating 5-minute periods of reperfusion (ischemic preconditioning). Then the coronary artery was occluded for 90 minutes followed by 6 hours of reperfusion. Infarct size, normalized by the risk area, in the ischemic preconditioning group was smaller than in the control group (42.6±3.6% in the control group versus 7.9±1.8% in the ischemic preconditioning group, P<.001). Myocardial ecto-5'-nucleotidase activity was increased after the ischemic preconditioning procedure but the increase in ecto-5'-nucleotidase was attenuated by inhibitors of protein kinase C (polymyxin B and GF109203X). Both polymyxin B and GF109203X blunted the infarct size–limiting effect of ischemic preconditioning (infarct size 33.1±6.9% and 35.1±6.4%, respectively). The infarct size–limiting effect was also blunted by an inhibitor of ecto-5'-nucleotidase. Transient administration of methoxamine mimicked the increase in ecto-5'-nucleotidase activity and the infarct size–limiting effect, both of which were abolished by inhibitors of protein kinase C.
Conclusions We conclude that activation of ecto-5'-nucleotidase and protein kinase C contributes to the infarct size–limiting effect of ischemic preconditioning.
Key Words: ecto-5'-nucleotidase • myocardial infarction • adenosine • receptors, adrenergic, alpha • ischemia
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