Faculty Collaboration Database

A novel antioxidant, EPC-K1, stimulates endothelial nitric oxide production and scavenges hydroxyl radicals. Circ J 2003 Dec;67(12):1046-52

Date

11/26/2003

Pubmed ID

14639022

DOI

10.1253/circj.67.1046

Scopus ID

2-s2.0-0344738766 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

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-K1 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-K1 (10(-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-K1 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 (10(-4) mol/L), but not by (D)-arginine (10 (-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(2)O(2) [0.56 mmol/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 endothelium-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 endothelial cell injury. These 2 independent and important actions are possible mechanisms by which EPC-K1 prevents reperfusion injury in the ischemic heart.

Author List

Takayama H, Hamner CE, Caccitolo JA, Hisamochi K, Pearson PJ, Schaff HV

Author

Paul Joseph Pearson MD, PhD Chief, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antioxidants
Arginine
Ascorbic Acid
Coronary Vessels
Dinoprost
Dogs
Endothelium, Vascular
Female
Free Radical Scavengers
Hydroxyl Radical
Male
Models, Animal
Nitric Oxide Synthase
Nitric Oxide Synthase Type III
Vasodilation
Vitamin E
omega-N-Methylarginine