A Novel Antioxidant, EPC-K1, Stimulates Endothelial Nitric Oxide Production and Scavenges Hydroxyl Radicals

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EPC-K1, a hydroxyl radical scavenger synthesized by phosphate linkage of vitamin E and vitamin C, prevents myocardial reperfusion injury in vivo; however, the direct effects of EPC-Kl on coronary arteries are unknown. These experiments were undertaken to define possible mechanisms through which EPC-K1 imparts its protective action on the coronary vasculature. EPC-Kl (l0^<-5> to 10^<-1> mg/ml) induced concentration-dependent relaxation in contracted canine coronary artery segments with endothelium, but no change in tension of arterial segments without endothelium (p<0.05, ANOVA). Endothelium-dependent relaxation to EPC-K 1 was inhibited by N^G-monomethyl-L-arginine (L-NMMA) (10^<-5>mol/L). Inhibition of relaxation by L-NMMA was reversed by the addition of L-arginine (l0^<-4>mol/L), but not by D-arginine (l0^<-4> mol/L). Subsequent exposure of canine coronary artery segments with intact endothelium to hydroxyl radicals for 30 min (generated by FeSO_4 [0.56 mmol/L]+H_2O_2 [0.56mmol/L]) impaired endothelium-dependent relaxation. However, pretreating the vascular segments with EPC-K1 (10^<-4>mg/ml) prevented hydroxyl radical-mediated endothelial cell injury and maintained endo-thelium-dependent relaxation. These experiments indicate that EPC-K1 stimulates the release of endothelium-derived nitric oxide, an endogenous vasodilator and inhibitor of platelet and leukocyte activation and adhesion, from the coronary artery endothelium. Additionally, EPC-K1 scavenges hydroxyl radicals that mediate endothehal cell injury. These 2 independent and important actions are possible mechanisms by which EPC-K1 prevents reperfusion injury in the ischemic heart. (Circ 12003; 67: 1046-1052
社団法人日本循環器学会の論文
2003-11-20

A Novel Antioxidant, EPC-K1, Stimulates Endothelial Nitric Oxide Production and Scavenges Hydroxyl Radicals

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