Limitation of myocardial infarct size by adenosine A1 receptor activation is abolished by protein kinase C inhibitors in the rabbit.
OBJECTIVE
The aim was to test whether infarct size limitation by adenosine A1 receptor activation is mediated by protein kinase C.


METHODS
In the first series of experiments, myocardial infarction was induced in rabbits under pentobarbitone anaesthesia by 30 min coronary artery occlusion and 3 h reperfusion. Rabbits were pretreated with no drugs (control). 1 mg.kg-1 of R(-)N6-2-phenylisopropyl adenosine (PIA), 50 micrograms.kg-1 of staurosporine (Stauro), 2.5 mg.kg-1 of polymyxin B (PolyB), and a combination of PIA and either Stauro or PolyB. Infarct size and the area at risk were determined by tetrazolium staining and fluorescent particles, respectively. In the second series of experiments, the inotropic response to 4 beta-phorbol 12-myristate 13-acetate (PMA) was assessed in rabbits with and without pretreatment using the same doses of Stauro and PolyB as those in the first series of experiments.


RESULTS
Infarct size expressed as percent of area at risk (%IS/AR) was significantly smaller in the PIA treated group than in the control: %IS/AR = 19.0(SEM 2.4)% v 37.7(4.0)%, P < 0.05. However, %IS/AR in the groups given Stauro [35.0(4.2)%], PolyB [37.9(3.2)%], PIA plus Stauro [34.9(3.9)%], and PIA plus PolyB [36.3(3.3)%] did not differ from the control value. PMA at the dose of 0.02 and 0.05 micrograms.kg-1 caused a dose dependent increase of the left ventricular dP/dtmax in the untreated rabbits. Such a positive inotropic response to PMA was not detected in rabbits pretreated with Stauro or PolyB, suggesting that the doses of the protein kinase C inhibitors were appropriate to block protein kinase C in the heart.


CONCLUSIONS
Infarct size limitation by A1 receptor stimulation is mediated by activation of protein kinase C in pentobarbitone anaesthetised rabbits.
Sakamoto
J
J
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Miura
T
T
Goto
M
M
Iimura
O
O
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010660:Phenylisopropyladenosine / Q000627:therapeutic use*; D011112:Polymyxin B / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011817:Rabbits; D019311:Staurosporine; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D010660:Phenylisopropyladenosine; D011493:Protein Kinase C; D019311:Staurosporine; D011112:Polymyxin B; D013755:Tetradecanoylphorbol Acetate