PKC inhibitors prevent endothelial dysfunction after myocardial ischemia-reperfusion in rats.
The intracellular mechanism for endothelial dysfunction after myocardial ischemia-reperfusion remains to be elucidated. It has been reported that activation of protein kinase C (PKC) occurs after myocardial ischemia-reperfusion and that the activation impairs endothelium-dependent relaxation. Thus we examined the role of PKC activation in the ischemia-reperfusion-induced endothelial dysfunction. Isolated rat hearts perfused with a constant flow were subjected to global ischemia for 15 min followed by reperfusion for 20 min. Coronary vascular responses to the endothelium-dependent vasodilators acetylcholine (ACh) and bradykinin (BK) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were examined before and after the ischemia-reperfusion. Endothelium-dependent relaxations to ACh and BK were impaired after the ischemia-reperfusion, whereas endothelium-independent relaxations to SNP were unaffected. Pretreatment with a PKC inhibitor, staurosporine, H7, or calphostin C, prevented the impairments. Phorbol 12-myristate 13-acetate, a PKC-activating phorbol ester, attenuated the relaxations to ACh and BK but not those to SNP. These results suggest that PKC activation may be involved in part in the ischemia-reperfusion-induced endothelial dysfunction.
Numaguchi
K
K
Research Institute of Angiocardiology, Kyushu University School of Medicine, Fukuoka Japan.
Shimokawa
H
H
Nakaike
R
R
Egashira
K
K
Takeshita
A
A
D000818:Animals; D065128:Endothelin Receptor Antagonists; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D004789:Enzyme Activation; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D010456:Peptides, Cyclic / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D011921:Rats, Inbred WKY; D015427:Reperfusion Injury / Q000503:physiopathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C072247:cyclo(Trp-Asp-Pro-Val-Leu)