We have previously demonstrated that cardioprotection induced by the infusion of a selective delta1-opioid agonist is mediated by the specific translocation of PKC-delta to the mitochondria in in vivo rat hearts and via opening of the mitochondrial
KATP channel. Ischemic preconditioning (IPC) is also thought to involve the translocation of specific
isoforms of PKC and
KATP channel activation. Therefore, we utilized the PKC-delta selective antagonist,
rottlerin, to assess the effect of inhibition of this
isozyme on cardioprotection induced by one-cycle of IPC prior to 30 minutes of
ischemia and 2 hours of reperfusion.
Infarct size (IS) was determined by tetrazolium
chloride staining and expressed as a percent of the area at risk (AAR). Non-preconditioned control animals had an IS/AAR of 59.7 +/- 1.6. IPC significantly reduced the extent of
myocardial infarction (6.3 +/- 1.4).
Rottlerin, 0.3 mg/kg, did not alter IS/AAR in control animals (55.0 +/- 5.6), and had no significant effect on IS/AAR in preconditioned animals (14.4 +/- 3.8). Additionally, we demonstrated, using a
luciferase-based assay to determine the rate of
ATP synthesis and state of mitochondrial bioenergetics, that IPC preserves
ATP synthesis in the ischemic myocardium and that this preservation is attenuated by the
isoform non-selective PKC inhibitor,
chelerythrine, but not by the delta-selective antagonist,
rottlerin. These data suggest that PKC-delta does not play an important role in IPC and that differences in
isoform importance are evident during pharmacological versus
ischemia-induced preconditioning.