Endothelial dysfunction associated with oxidative stress in human.

The imbalance in pro- and anti-oxidant activity causes endothelial dysfunction, which precedes and exacerbates atherosclerosis. LDL-apheresis improves ischemic symptom in patients with hypercholesterolemia and regresses atherosclerosis. Whereas, patients who undergo hemodialysis experience accelerated atherosclerosis and premature death even though their cholesterol level is known to be normal. We investigated the association between oxidative modification and endothelial function during a single session of blood purification therapies, LDL-apheresis and hemodialysis. To examine the effect of a single session of LDL-apheresis on endothelial function in patients with hypercholesterolemia, we measured forearm blood flow (FBF) by strain gauge plethysmography before and after LDL-apheresis, while infusing acetylcholine (ACh) and sodium nitroprusside (SNP). The single session of LDL-apheresis reduced oxidized-LDL. Although ACh and SNP increased FBF dose-dependently before and after LDL-apheresis, ACh response was significantly augmented without changes in responses to SNP. The plasma level of oxidized LDL correlated with the degree of ACh-induced vasodilatation. To examine the effect of a single session of hemodialysis on endothelial function in patients with end stage renal disease, we estimated flow-mediated vasodilation (FMD) during reactive hyperemia using a high-resolution ultrasonography, before and after a single session of hemodialysis. We also investigated the effect of anti-oxidative modification during hemodialysis using an a-tocopherol acetate-coated or a non-coated cellulose dialyzer. Non-specific endothelium independent vasodilation was measured after sublingual glyceryltrinitrate spray (GTN; 0.3 mg) administration in each session. A single session of hemodialysis increased plasma level of oxidized LDL. Although hemodialysis treatment did not affect GTN-induced vasodilation, a single session of hemodialysis impaired the endothelium-dependent vasodilation. Treatment with vitamin E-coated-dialyzer restored endothelium-dependent vasodilation, which was accompanied by decrease in oxidized LDL. Thus, endothelial function was impaired by acute increase in oxidative stress and was restored by anti-oxidant therapy. Our results suggest the importance of controlling oxidative stress in addition to classical risk factors to preserve human endothelial function.