Role of activation of protein kinase C in the infarct size-limiting effect of ischemic preconditioning through activation of ecto-5'-nucleotidase.
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.


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.
Kitakaze
M
M
First Department of Medicine, Osaka (Japan) University School of Medicine, Suita, Japan.
Node
K
K
Minamino
T
T
Komamura
K
K
Funaya
H
H
Shinozaki
Y
Y
Chujo
M
M
Mori
H
H
Inoue
M
M
Hori
M
M
Kamada
T
T
D015720:5'-Nucleotidase / Q000378:metabolism*; D000818:Animals; D004285:Dogs; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics; D008729:Methoxamine / Q000494:pharmacology; D009203:Myocardial Infarction / Q000201:enzymology* / Q000209:etiology* / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
D004791:Enzyme Inhibitors; D011493:Protein Kinase C; D015720:5'-Nucleotidase; D008729:Methoxamine